<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/NCT03274076</url>
  </required_header>
  <id_info>
    <org_study_id>HUM00131837</org_study_id>
    <nct_id>NCT03274076</nct_id>
  </id_info>
  <brief_title>Evaluation of Tofacitinib in Early Diffuse Cutaneous Systemic Sclerosis (dcSSc)</brief_title>
  <acronym>TOFA-SSc</acronym>
  <official_title>Evaluation of Tofacitinib in Early Diffuse Cutaneous Systemic Sclerosis (dcSSc): A Phase I/II Two Center Safety and Tolerability Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Michigan</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This Phase I/II placebo controlled trial will evaluate tofacitinib in subjects with diffuse&#xD;
      cutaneous systemic scleroderma (dcSSc). This trial is intended to provide safety, and&#xD;
      tolerability data in participants with dcSSc when dosed to target exposures similar to that&#xD;
      used in adult participants with rheumatoid arthritis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this clinical research study is to evaluate the safety, tolerability and&#xD;
      efficacy of treatment with tofacitinib (study drug) versus placebo (a substance with no&#xD;
      active ingredients and therefore may have no treatment benefit) in people with diffuse&#xD;
      cutaneous systemic scleroderma. Subjects will be randomized to tofacitinib vs. placebo in a&#xD;
      2:1 ratio at 5 mg twice a day for 24 weeks. Subjects will then be offered to participate in&#xD;
      an open label phase during which they will receive tofacitinib 5 mg twice a day for 24 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 25, 2017</start_date>
  <completion_date type="Actual">November 15, 2019</completion_date>
  <primary_completion_date type="Actual">April 8, 2019</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Eligible subjects will be randomized to tofacitinib or placebo in a 2:1 manner.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>The study staff (with the exception of the study pharmacist) and the patient are blinded to the treatment assignment.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants Who Experience Grade 3 or Higher Adverse Events That Occur at or Before Week 24</measure>
    <time_frame>24 weeks</time_frame>
    <description>Primary outcome is met if any participants experience a grade 3 or higher event prior to Week 24. A grade 3 AE would constitute as &quot;severe&quot;. Grading was following using CTCAE v 4.03.&#xD;
Note that the planned statistical analysis (Fisher's exact test) could not be performed because there were no events.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Grade 3 (Severe) or Higher Adverse Events That Occur Throughout the Study</measure>
    <time_frame>Week 12, 24, 36, and 48</time_frame>
    <description>Grade 3 or higher adverse events (AEs) assessed throughout the study ( 48 weeks). A grade 3 AE would constitute as &quot;severe&quot;. Grading was following using CTCAE v 4.03.&#xD;
Note that the planned statistical analysis (calculation of rate ratio and 90% CI) could not be performed at Weeks 12 and 24 due to no events, and could not be performed at Week 36 because there were no events in the placebo group (denominator).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Grade 2 (Moderate) or Higher Adverse Events That Occur Throughout the Study</measure>
    <time_frame>Week: 12, 24, 36, and 48</time_frame>
    <description>Grade 2 or higher assessed 12 weeks apart. Grade 2 AEs are determined as &quot; moderate&quot;. Grading was performed following CTCAE v 4.03 guidance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Adverse Events of Special Interest (AESI) Throughout the Study</measure>
    <time_frame>Weeks 12, 24, 36 and 48</time_frame>
    <description>AESI are pre-defined adverse events as indicated in the protocol. They include: infections, stomach perforations, malignancy, herpes zoster and lab abnormalities.&#xD;
Note that the planned statistical analysis (calculation of rate ratio and 90% CI) could not be performed at Weeks 12 and 24 because there were no events in placebo group (denominator).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Modified Rodnan Skin Score (mRSS)</measure>
    <time_frame>Change from Baseline at weeks: 12, 24, 36, and 48</time_frame>
    <description>The Modified Rodnan Skin Score (mRSS) is a measure of skin thickness. Skin thickness in 17 anatomic areas was rated on a 0-3 scale and scores are summed to obtain the mRSS (range from 0 - 51), with higher mRSS scores indicating worse disease activity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Provisional American College of Rheumatology Combined Response Index (CRISS) Systemic Sclerosis</measure>
    <time_frame>Week:12, 24, and 48</time_frame>
    <description>CRISS components included the following domains: modified Rodnan skin score, forced vital capacity percent predicted, Physician Global Assessment, Patient Global Assessment, and Health Assessment Questionnaire Disability-Index. An algorithm determines the predicted probability of improvement from baseline by incorporating change in the mRSS, FVC percent predicted, Physician and Patient Global Assessments, and HAQ-DI. The outcome is a continuous variable between 0.0 and 1.0 (0 - 100%). A cut-off at 0.6 in the predicted probability of being improved has yielded the smallest misclassification error. Subjects are not considered improved if, between Visit 1 and 6, they develop new: 1) renal crisis; 2) decline in FVC% predicted by 15% (relative) from baseline and confirmed after 1 month; or 3) left ventricular failure (systolic ejection fraction &lt; 45%) or pulmonary artery hypertension. Higher CRISS scores indicates improvement.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Systemic Sclerosis</condition>
  <condition>Scleroderma</condition>
  <arm_group>
    <arm_group_label>Tofacitinib</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>5mg Tofacitinib twice a day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>5mg Placebo twice a day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tofacitinib</intervention_name>
    <description>Oral medication tofacitinib 5 mg twice a day for 24 weeks.</description>
    <arm_group_label>Tofacitinib</arm_group_label>
    <other_name>Xeljanz</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <description>Oral Placebo 5 mg twice a day for 24 weeks</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Diagnosis of systemic sclerosis (SSc), as classified using the 2013 American College&#xD;
             of Rheumatology/ European Union League Against Rheumatism classification of SSc.&#xD;
&#xD;
          2. Diffuse Cutaneous Systemic Sclerosis (dcSSc) as defined by 2001 LeRoy and Medsger&#xD;
&#xD;
          3. Disease duration ≤ 60 months (defined as time from the first non-Raynaud phenomenon&#xD;
             manifestation)&#xD;
&#xD;
          4. Modified Rodnan Skin Score (mRSS) units ≥ 10 and ≤ 45 at screening.&#xD;
&#xD;
          5. Agreement to receive varicella-zoster vaccination (Zostavax®) or have received&#xD;
             vaccination prior to screening.&#xD;
&#xD;
          6. Oral corticosteroids (≤ 10 mg/day of prednisone or equivalent) are permitted if the&#xD;
             patient is on a stable dose regimen for ≥ 2 weeks prior to and including the baseline&#xD;
             visit.&#xD;
&#xD;
          7. Ability to provide informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Rheumatic disease other than dcSSc; it is acceptable to include patients with&#xD;
             fibromyalgia, Sjogren syndrome, and scleroderma-associated myopathy&#xD;
&#xD;
          2. Limited cutaneous SSc or sine scleroderma&#xD;
&#xD;
          3. Major surgery (including joint surgery) within 8 weeks prior to baseline.&#xD;
&#xD;
          4. Any infected ulcer at screening&#xD;
&#xD;
          5. Subjects with any serious bacterial infection within the last 3 months, unless treated&#xD;
             and resolved with antibiotics, or any chronic bacterial infection (e.g., chronic&#xD;
             pyelonephritis, osteomyelitis, or bronchiectasis)&#xD;
&#xD;
          6. Oral corticosteroids &gt;10 mg/day of prednisone or equivalent.&#xD;
&#xD;
          7. Hydroxychloroquine &gt;400 mg/day, methotrexate &gt;25 mg/week, D-Penicillamine &gt;1000mg/day&#xD;
             or mycophenolate mofetil &gt; 2 grams/day prior to baseline. **Subjects can be on&#xD;
             combination therapy of hydroxychloroquine and methotrexate or hydroxychloroquine and&#xD;
             mycophenolate mofetil and must have been on a stable dose for at least 1 month prior&#xD;
             to baseline visit.&#xD;
&#xD;
          8. Prior history of treatment in the 3 months prior to baseline with biological disease&#xD;
             modifying anti-rheumatic drugs (DMARDs)potent immunosuppressants such as cyclosporine&#xD;
             and azathioprine&#xD;
&#xD;
          9. Treatment with etanercept within ≤ 2 weeks of baseline: infliximab, certolizumab,&#xD;
             golimumab, abatacept, tocilizumab, or adalimumab within ≤ 8 weeks of baseline; and&#xD;
             anakinra within ≤ 1 week prior to the baseline visit.&#xD;
&#xD;
         10. Intravenous corticosteroids within 2 weeks prior to baseline visit.&#xD;
&#xD;
         11. Treatment with any investigational agent ≤ 4 weeks prior to baseline (or 5 half-lives&#xD;
             of the investigational drug, whichever is longer)&#xD;
&#xD;
         12. Other investigational or marketed biologics with immunomodulatory properties within 3&#xD;
             months prior to baseline.&#xD;
&#xD;
         13. Treatment with anti-CD20 6 months prior to baseline and B cell counts &lt;LLN&#xD;
&#xD;
         14. Any prior treatment with cell-depleting therapies other than anti-CD20 such as&#xD;
             CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19&#xD;
&#xD;
         15. Any prior treatment with chlorambucil, bone marrow transplantation, or total lymphoid&#xD;
             irradiation&#xD;
&#xD;
         16. Vaccinated or exposed to a live/attenuated vaccine (other than Zostavax®) ≤ 6 weeks&#xD;
             prior to baseline; or is expected to be vaccinated or to have household exposure to&#xD;
             these vaccines during treatment or during the 6 weeks following discontinuation of&#xD;
             study medication. (**See additional inclusion for obtaining Zostavax® prior to&#xD;
             entering the study)&#xD;
&#xD;
         17. Pulmonary disease with Forced Vital Capacity (FVC) ≤ 50% of predicted, or Diffusing&#xD;
             capacity of the lungs for carbon monoxide (DLCO),(uncorrected for hemoglobin) ≤ 40% of&#xD;
             predicted&#xD;
&#xD;
         18. History of pulmonary arterial hypertension (PAH) with mean PAP&gt; 30 mmHg on right heart&#xD;
             catheterization requiring subcutaneous or intravenous prostacyclin or dual use of oral&#xD;
             PAH therapies&#xD;
&#xD;
         19. Subjects at risk for tuberculosis (TB):&#xD;
&#xD;
             A. Specifically excluded from this study will be participants with a history of active&#xD;
             TB within the last 3 years, even if it was treated; a history of active TB greater&#xD;
             than 3 years ago, unless there is documentation that the prior anti-TB treatment was&#xD;
             appropriate in duration and type; current clinical, radiographic, or laboratory&#xD;
             evidence of active TB; (TB results within 30 days of screening will be accepted and&#xD;
             will not to be repeated. B. Latent TB at or within 30 days of screening, history of or&#xD;
             current positive purified protein derivative tuberculin skin test (PPD) ( &gt;5mm&#xD;
             induration, regardless of Bacille Calmette Guerin [BCG] vaccine and/or QuantiFERON&#xD;
             Gold, a negative chest x-ray, and no symptoms or risk factors), unless one month of&#xD;
             prophylaxis has been completed prior to inclusion&#xD;
&#xD;
               -  An indeterminate QuantiFERON® unless followed by a subsequent negative PPD or&#xD;
                  negative QuantiFERON® or a consultation with and clearance by local infectious&#xD;
                  disease (ID) department is required.&#xD;
&#xD;
         20. Positive for hepatitis B surface antigen at or within 30 days of screening&#xD;
&#xD;
         21. Positive for hepatitis C antigen at or within 30 days of screening&#xD;
&#xD;
         22. Current or recent history of uncontrolled clinically significant renal, hepatic,&#xD;
             hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurologic&#xD;
             disease.&#xD;
&#xD;
         23. History of human immunodeficiency virus (HIV), (as determined by medical records or&#xD;
             patient reported).&#xD;
&#xD;
         24. History of diverticulitis or chronic, ulcerative lower gastrointestinal (GI) disease&#xD;
             such as Crohns disease, ulcerative colitis, or other symptomatic, lower GI conditions&#xD;
             that might predispose a patient to perforations.&#xD;
&#xD;
         25. Pregnant or breastfeeding female subjects; and female subjects of childbearing&#xD;
             potential who are unwilling or unable to use a highly effective method of&#xD;
             contraception as outlined in the protocol for the duration of the study and for at&#xD;
             least 28 days after discontinuation of study drug.&#xD;
&#xD;
         26. Severe acute or chronic medical or psychiatric condition or laboratory abnormality&#xD;
             that may increase risk associated with study participation and in the judgment of the&#xD;
             investigator would make the subject inappropriate for entry into this study.&#xD;
&#xD;
         27. History of systemic sclerosis (SSc) Renal Crisis within the 6 months prior to&#xD;
             baseline.&#xD;
&#xD;
         28. Any of the following lab results at screening:&#xD;
&#xD;
               -  Hemoglobin &lt;9 g/dL or Hematocrit &lt;30%&#xD;
&#xD;
               -  White Blood Cell count &lt;3.0 x 109/L;&#xD;
&#xD;
               -  Absolute Neutrophil count &lt;1.2 x 109/L;&#xD;
&#xD;
               -  White Blood Cell count &lt;3.0 x 109/L;&#xD;
&#xD;
               -  Absolute Neutrophil count &lt;1.2 x 109/L;&#xD;
&#xD;
               -  Platelet count &lt;100 x 109/L;&#xD;
&#xD;
               -  Absolute Lymphocyte count &lt;0.75 x 109/L.&#xD;
&#xD;
               -  ALT or AST &gt; 1.5 × the upper limit of normal (ULN) of normal at screening or any&#xD;
                  uncontrolled clinically significant laboratory abnormality that would affect&#xD;
                  interpretation of study data or the patient's participation in the study&#xD;
&#xD;
               -  Total bilirubin &gt; upper limit of normal (ULN) at Screening.&#xD;
&#xD;
               -  Estimated glomerular filtration rate [GFR] &lt;40mL/min/1.73 m2&#xD;
&#xD;
         29. Prior rituximab use without documentation of normalized b cell counts.&#xD;
&#xD;
         30. History of recurrent (more than one episode) herpes zoster or disseminated (at least&#xD;
             one episode) herpes zoster, or disseminated (at least one episode) herpes simplex&#xD;
&#xD;
         31. History of any lymphoproliferative disorder, such as Epstein Barr Virus (EBV) related&#xD;
             lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms&#xD;
             suggestive of current lymphatic disease.&#xD;
&#xD;
         32. History of any malignancy in the last 5 years with the exception of adequately treated&#xD;
             or excised basal cell or squamous cell or cervical cancer in situ.&#xD;
&#xD;
         33. Significant trauma or surgery procedure within 1 month prior to first dose of study&#xD;
             drug.&#xD;
&#xD;
         34. History of alcohol or substance abuse, unless in full remission for greater than 6&#xD;
             months prior to first dose of study drug.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dinesh Khanna, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15261</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>August 28, 2017</study_first_submitted>
  <study_first_submitted_qc>September 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 6, 2017</study_first_posted>
  <results_first_submitted>March 31, 2020</results_first_submitted>
  <results_first_submitted_qc>April 28, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">May 8, 2020</results_first_posted>
  <last_update_submitted>April 28, 2020</last_update_submitted>
  <last_update_submitted_qc>April 28, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Michigan</investigator_affiliation>
    <investigator_full_name>Dinesh Khanna, MD, MS</investigator_full_name>
    <investigator_title>Frederick G L Huetwell Professor of Rheumatology and Professor of Internal Medicine, Medical School</investigator_title>
  </responsible_party>
  <keyword>diffuse</keyword>
  <keyword>scleroderma</keyword>
  <keyword>systemic sclerosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Scleroderma, Systemic</mesh_term>
    <mesh_term>Scleroderma, Diffuse</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tofacitinib</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <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>March 25, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/76/NCT03274076/SAP_001.pdf</document_url>
    </provided_document>
    <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>September 17, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/76/NCT03274076/Prot_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were recruited from University of Michigan and University of Pittsburgh Scleroderma clinics. The recruitment period began in September 2017 and ended with the last participant randomization in October 2018.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Tofacitinib Double Blind 0-24 Weeks</title>
          <description>Participants treated with an oral medication tofacitinib 5 mg twice daily for 24 weeks with option to enter 24 weeks of open label tofacitinib.</description>
        </group>
        <group group_id="P2">
          <title>Placebo Double Blind 0-24 Weeks</title>
          <description>Participants treated with an oral placebo 5 mg twice daily for 24 weeks with option to enter 24 weeks of open label tofacitinib.</description>
        </group>
        <group group_id="P3">
          <title>Tofacitinib to Tofacitinib Open Label 24-48 Weeks</title>
          <description>Post double blind completion, participants receive 5mg tofacitinib twice daily for 24 weeks.</description>
        </group>
        <group group_id="P4">
          <title>Placebo to Tofacitinib Open Label 24-48 Weeks</title>
          <description>Post double blind completion, participants receive 5mg tofacitinib twice daily for 24 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>24 Weeks Double Blind</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>24 Weeks Open Label</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Tofacitinib Double Blind 0-24 Weeks</title>
          <description>Participants treated with an oral medication tofacitinib 5 mg twice daily for 24 weeks with option to enter 24 weeks of open label tofacitinib.</description>
        </group>
        <group group_id="B2">
          <title>Placebo Double Blind 0-24 Weeks</title>
          <description>Participants treated with oral placebo tablet 5 mg twice a daily for 24 weeks with option to enter 24 weeks of open label tofacitinib.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
            <count group_id="B2" value="5"/>
            <count group_id="B3" value="15"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="46.2" spread="13.9"/>
                    <measurement group_id="B2" value="60.0" spread="9.7"/>
                    <measurement group_id="B3" value="50.8" spread="14.0"/>
                  </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="7"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <description>Study was conducted only in the United States</description>
          <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="10"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Disease Duration</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2.0" spread="1.3"/>
                    <measurement group_id="B2" value="2.4" spread="1.2"/>
                    <measurement group_id="B3" value="2.1" spread="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline Modified Rodnan Skin Score (mRSS</title>
          <description>The Modified Rodnan Skin Score (mRSS) is a measure of skin thickness. Skin thickness in 17 anatomic areas was rated on a 0-3 scale and scores are summed to obtain the mRSS (range from 0 - 51), with higher mRSS scores indicating worse skin involvement.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22.7" spread="9.3"/>
                    <measurement group_id="B2" value="24.4" spread="6.9"/>
                    <measurement group_id="B3" value="23.3" spread="8.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Forced Vital Capacity (FVC) % Predicted</title>
          <description>Forced Vital Capacity (FVC) is the amount of air that can be forcibly exhaled after a full breath and is a measure of lung function. Predicted FVC was based on institutional standards. Values lower than 80% are indicated as abnormal.</description>
          <units>percent predicted</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="90.7" spread="16.5"/>
                    <measurement group_id="B2" value="83.8" spread="17.5"/>
                    <measurement group_id="B3" value="88.4" spread="16.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diffusion in liters of carbon monoxide (DLCO) % Predict</title>
          <description>Diffusion in liters of carbon monoxide (DLCO) is a measure of lung function. Predicted values for DLCO were computed using the Crapo Morris equations. Values lower than 80% are considered abnormal.</description>
          <units>percent predicted</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="82.4" spread="19.7"/>
                    <measurement group_id="B2" value="92.0" spread="20.5"/>
                    <measurement group_id="B3" value="85.6" spread="19.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Health Assessment Questionnaire - Disability Index (HAQ-DI)</title>
          <description>Health Assessment Questionnaire - Disability Index (HAQ-DI) is a self-reported questionnaire of functionality that includes questions in 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities). The final score ranges from 0 to 3, where a higher HAQ-DI score indicates a worse outcome.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.01" spread="0.6"/>
                    <measurement group_id="B2" value="0.80" spread="0.5"/>
                    <measurement group_id="B3" value="0.98" spread=".59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Proportion of Participants with Tender Friction Rubs</title>
          <description>Tender Friction Rubs are noticeable upon exam and show as grating sensations to the fibrinous deposits on the surface of the tendon sheaths and overlying fascia</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Proportion of Participants with Large Joint Contractures</title>
          <description>Large joint contracture is caused by shortening of muscles, tendons, ligaments, and joint capsules or by heterotopic ossification that affect the large joints.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Proportion of Participants with Background Immunosuppressive</title>
          <description>Background medications included within the immunosuppressive group included: methotrexate and mycophenolic acid.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Proportion of Participants Using Prednisone</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Proportion of Participants with Interstitial Lung Disease on High-resolution computed tomography</title>
          <description>High-resolution computed tomography (HRCT) is a type of computed tomography with specific techniques to enhance image resolution. It is used in the diagnosis of various health problems, though most commonly for diseases of the lung.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Proportion of Participants with Small Joint Contractures</title>
          <description>Small joint contracture is caused by shortening of muscles, tendons, ligaments, and joint capsules or by heterotopic ossification that affect the small joints.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Who Experience Grade 3 or Higher Adverse Events That Occur at or Before Week 24</title>
        <description>Primary outcome is met if any participants experience a grade 3 or higher event prior to Week 24. A grade 3 AE would constitute as &quot;severe&quot;. Grading was following using CTCAE v 4.03.&#xD;
Note that the planned statistical analysis (Fisher's exact test) could not be performed because there were no events.</description>
        <time_frame>24 weeks</time_frame>
        <population>All participants were included in this analysis although 1 placebo participant withdrew prior to week 24. They remained in the intent to treat population.</population>
        <group_list>
          <group group_id="O1">
            <title>Tofacitinib Double Blind 0-24 Weeks</title>
            <description>Participants treated with an oral medication tofacitinib 5 mg twice daily for 24 weeks with option to enter 24 weeks of open label tofacitinib.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Double Blind 0-24 Weeks</title>
            <description>Participants treated with oral placebo tablet 5 mg twice a day for 24 weeks with option to enter 24 weeks of open label tofacitinib.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Experience Grade 3 or Higher Adverse Events That Occur at or Before Week 24</title>
          <description>Primary outcome is met if any participants experience a grade 3 or higher event prior to Week 24. A grade 3 AE would constitute as &quot;severe&quot;. Grading was following using CTCAE v 4.03.&#xD;
Note that the planned statistical analysis (Fisher's exact test) could not be performed because there were no events.</description>
          <population>All participants were included in this analysis although 1 placebo participant withdrew prior to week 24. They remained in the intent to treat population.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Grade 3 (Severe) or Higher Adverse Events That Occur Throughout the Study</title>
        <description>Grade 3 or higher adverse events (AEs) assessed throughout the study ( 48 weeks). A grade 3 AE would constitute as &quot;severe&quot;. Grading was following using CTCAE v 4.03.&#xD;
Note that the planned statistical analysis (calculation of rate ratio and 90% CI) could not be performed at Weeks 12 and 24 due to no events, and could not be performed at Week 36 because there were no events in the placebo group (denominator).</description>
        <time_frame>Week 12, 24, 36, and 48</time_frame>
        <population>One placebo participant withdrew prior to week 24. 1 additional placebo participant and 2 tofacitinib participants withdrew prior to week 48 but after completing week 24 and entering the open label portion.</population>
        <group_list>
          <group group_id="O1">
            <title>Tofacitinib Double Blind 0-24 Weeks</title>
            <description>Participants treated with an oral medication tofacitinib 5mg twice daily for 24 weeks with option to enter 24 weeks of open label tofacitinib.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Double Blind 0-24 Weeks</title>
            <description>Participants treated with an oral placebo tablet 5mg twice daily for 24 weeks with option to enter 24 weeks of open label tofacitinib.</description>
          </group>
          <group group_id="O3">
            <title>Tofacitinib to Tofacitinib Open Label 24-48 Weeks</title>
            <description>Post double blind completion, participants receive 5mg tofacitinib twice daily for 24 weeks.</description>
          </group>
          <group group_id="O4">
            <title>Placebo to Tofacitinib Open Label 24-48 Weeks</title>
            <description>Post double blind completion, participants receive 5mg tofacitinib twice daily for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Grade 3 (Severe) or Higher Adverse Events That Occur Throughout the Study</title>
          <description>Grade 3 or higher adverse events (AEs) assessed throughout the study ( 48 weeks). A grade 3 AE would constitute as &quot;severe&quot;. Grading was following using CTCAE v 4.03.&#xD;
Note that the planned statistical analysis (calculation of rate ratio and 90% CI) could not be performed at Weeks 12 and 24 due to no events, and could not be performed at Week 36 because there were no events in the placebo group (denominator).</description>
          <population>One placebo participant withdrew prior to week 24. 1 additional placebo participant and 2 tofacitinib participants withdrew prior to week 48 but after completing week 24 and entering the open label portion.</population>
          <units>Adverse Events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="4"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 36</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="8"/>
                    <count group_id="O4" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="8"/>
                    <count group_id="O4" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>H0: Rate of grade 3 (severe) or higher adverse events that occur throughout week 48 in Placebo = Rate of grade 3 (severe) or higher adverse events that occur throughout week 48 in Tofacitinib.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Rate ratio</param_type>
            <param_value>1.25</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.19</ci_lower_limit>
            <ci_upper_limit>8.33</ci_upper_limit>
            <estimate_desc>Tofacitinib represents the numerator, and placebo represents the denominator.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Grade 2 (Moderate) or Higher Adverse Events That Occur Throughout the Study</title>
        <description>Grade 2 or higher assessed 12 weeks apart. Grade 2 AEs are determined as &quot; moderate&quot;. Grading was performed following CTCAE v 4.03 guidance.</description>
        <time_frame>Week: 12, 24, 36, and 48</time_frame>
        <population>One placebo participant withdrew prior to week 24. 1 additional placebo participant and 2 tofacitinib participants withdrew prior to week 48 but after completing week 24.</population>
        <group_list>
          <group group_id="O1">
            <title>Tofacitinib Double Blind 0-24 Weeks</title>
            <description>Participants treated with an oral medication tofacitinib 5mg twice daily for 24 weeks with option to enter 24 weeks of open label tofacitinib.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Double Blind 0-24 Weeks</title>
            <description>Participants treated with an oral placebo tablet 5mg twice daily for 24 weeks with option to enter 24 weeks of open label tofacitinib.</description>
          </group>
          <group group_id="O3">
            <title>Tofacitinib to Tofacitinib Open Label 24-48 Weeks</title>
            <description>Post double blind completion, participants receive 5 mg tofacitinib twice daily for 24 weeks.</description>
          </group>
          <group group_id="O4">
            <title>Placebo to Tofacitinib Open Label 24-48 Weeks</title>
            <description>Post double blind completion, participants receive 5 mg tofacitinib twice daily for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Grade 2 (Moderate) or Higher Adverse Events That Occur Throughout the Study</title>
          <description>Grade 2 or higher assessed 12 weeks apart. Grade 2 AEs are determined as &quot; moderate&quot;. Grading was performed following CTCAE v 4.03 guidance.</description>
          <population>One placebo participant withdrew prior to week 24. 1 additional placebo participant and 2 tofacitinib participants withdrew prior to week 48 but after completing week 24.</population>
          <units>Adverse Events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="4"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 36</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="8"/>
                    <count group_id="O4" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="14"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="8"/>
                    <count group_id="O4" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>H0: Rate of grade 2 (moderate) or higher adverse events that occur throughout week 12 in Placebo = Rate of grade 2 (moderate) or higher adverse events that occur throughout week 12 in Tofacitinib</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Rate ratio</param_type>
            <param_value>0.65</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.25</ci_lower_limit>
            <ci_upper_limit>1.71</ci_upper_limit>
            <estimate_desc>Tofacitinib represents the numerator, and Placebo represents the denominator.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>H0: Rate of grade 2 (moderate) or higher adverse events that occur throughout week 24 in Placebo = Rate of grade 2 (moderate) or higher adverse events that occur throughout week 24 in Tofacitinib</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Rate ratio</param_type>
            <param_value>0.53</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.26</ci_lower_limit>
            <ci_upper_limit>1.07</ci_upper_limit>
            <estimate_desc>Tofacitinib represents the numerator, and Placebo represents the denominator.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>H0: Rate of grade 2 (moderate) or higher adverse events that occur throughout week 36 in Placebo = Rate of grade 2 (moderate) or higher adverse events that occur throughout week 36 in Tofacitinib</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Rate ratio</param_type>
            <param_value>0.85</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.49</ci_lower_limit>
            <ci_upper_limit>1.49</ci_upper_limit>
            <estimate_desc>Tofacitinib represents the numerator, and Placebo represents the denominator.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>H0: Rate of grade 2 (moderate) or higher adverse events that occur throughout week 48 in Placebo = Rate of grade 2 (moderate) or higher adverse events that occur throughout week 48 in Tofacitinib</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Rate ratio</param_type>
            <param_value>0.89</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.52</ci_lower_limit>
            <ci_upper_limit>1.52</ci_upper_limit>
            <estimate_desc>Tofacitinib represents the numerator, and Placebo represents the denominator.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Adverse Events of Special Interest (AESI) Throughout the Study</title>
        <description>AESI are pre-defined adverse events as indicated in the protocol. They include: infections, stomach perforations, malignancy, herpes zoster and lab abnormalities.&#xD;
Note that the planned statistical analysis (calculation of rate ratio and 90% CI) could not be performed at Weeks 12 and 24 because there were no events in placebo group (denominator).</description>
        <time_frame>Weeks 12, 24, 36 and 48</time_frame>
        <population>Placebo participant withdrew prior to week 24. 1 additional placebo participant and 2 tofacitinib participants withdrew prior to week 48.</population>
        <group_list>
          <group group_id="O1">
            <title>Tofacitinib Double Blind 0 - 24 Weeks</title>
            <description>Participants treated with an oral medication tofacitinib 5mg twice daily for 24 weeks with option to enter 24 weeks of open label tofacitinib.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Double Blind 0 - 24 Weeks</title>
            <description>Participants treated with an oral placebo tablet 5mg twice daily for 24 weeks with option to enter 24 weeks of open label tofacitinib.</description>
          </group>
          <group group_id="O3">
            <title>Tofacitinib to Tofacitinib Open Label 24-48 Weeks</title>
            <description>Post double blind completion, participants receive 5mg tofacitinib twice daily for 24 weeks.</description>
          </group>
          <group group_id="O4">
            <title>Placebo to Tofacitinib Open Label 24-48 Weeks</title>
            <description>Post double blind completion, participants receive 5mg tofacitinib twice daily for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Adverse Events of Special Interest (AESI) Throughout the Study</title>
          <description>AESI are pre-defined adverse events as indicated in the protocol. They include: infections, stomach perforations, malignancy, herpes zoster and lab abnormalities.&#xD;
Note that the planned statistical analysis (calculation of rate ratio and 90% CI) could not be performed at Weeks 12 and 24 because there were no events in placebo group (denominator).</description>
          <population>Placebo participant withdrew prior to week 24. 1 additional placebo participant and 2 tofacitinib participants withdrew prior to week 48.</population>
          <units>Adverse Events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 36</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="8"/>
                    <count group_id="O4" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="8"/>
                    <count group_id="O4" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>H0: Rate of adverse events of special interest throughout week 36 in Placebo = Rate of adverse events of special interest throughout week 36 in Tofacitinib</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Rate ratio</param_type>
            <param_value>3.85</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.68</ci_lower_limit>
            <ci_upper_limit>21.77</ci_upper_limit>
            <estimate_desc>Tofacitinib represents the numerator, and Placebo represents the denominator.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>H0: Rate of adverse events of special interest throughout week 48 in Placebo = Rate of adverse events of special interest throughout week 48 in Tofacitinib</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Rate ratio</param_type>
            <param_value>1.87</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.5169</ci_lower_limit>
            <ci_upper_limit>6.7652</ci_upper_limit>
            <estimate_desc>Tofacitinib represents the numerator, and Placebo represents the denominator.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Modified Rodnan Skin Score (mRSS)</title>
        <description>The Modified Rodnan Skin Score (mRSS) is a measure of skin thickness. Skin thickness in 17 anatomic areas was rated on a 0-3 scale and scores are summed to obtain the mRSS (range from 0 - 51), with higher mRSS scores indicating worse disease activity</description>
        <time_frame>Change from Baseline at weeks: 12, 24, 36, and 48</time_frame>
        <population>Placebo participant withdrew prior to week 24. 1 additional placebo participant and 2 tofacitinib participants withdrew prior to week 48.</population>
        <group_list>
          <group group_id="O1">
            <title>Tofacitinib Double Blind 0-24 Weeks</title>
            <description>.Participants treated with an oral medication tofacitinib 5mg twice daily for 24 weeks with option to enter 24 weeks of open label tofacitinib.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Double Blind 0-24 Weeks</title>
            <description>Participants treated with an oral placebo tablet 5mg twice daily for 24 weeks with option to enter 24 weeks of open label tofacitinib.</description>
          </group>
          <group group_id="O3">
            <title>Tofacitinib (DB Tofacitinib) Open Label 24 - 48 Weeks</title>
            <description>Post double blind completion, participants receive 5mg tofacitinib twice daily for 24 weeks.</description>
          </group>
          <group group_id="O4">
            <title>Tofacitinib (DB Placebo) Open Label 24-48 Weeks</title>
            <description>Post double blind completion, participants receive 5mg tofacitinib twice daily for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Modified Rodnan Skin Score (mRSS)</title>
          <description>The Modified Rodnan Skin Score (mRSS) is a measure of skin thickness. Skin thickness in 17 anatomic areas was rated on a 0-3 scale and scores are summed to obtain the mRSS (range from 0 - 51), with higher mRSS scores indicating worse disease activity</description>
          <population>Placebo participant withdrew prior to week 24. 1 additional placebo participant and 2 tofacitinib participants withdrew prior to week 48.</population>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2" lower_limit="-4" upper_limit="-1"/>
                    <measurement group_id="O2" value="0.5" lower_limit="-2" upper_limit="4.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.5" lower_limit="-6" upper_limit="-1"/>
                    <measurement group_id="O2" value="-2.5" lower_limit="-7.5" upper_limit="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 36</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="8"/>
                    <count group_id="O4" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="-10" lower_limit="-12" upper_limit="-4"/>
                    <measurement group_id="O4" value="-6" lower_limit="-9.5" upper_limit="-2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="8"/>
                    <count group_id="O4" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="-12.5" lower_limit="-15.5" upper_limit="-5.5"/>
                    <measurement group_id="O4" value="-9" lower_limit="-11" upper_limit="-9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>H0: The absolute change in mRSS from week 0 to week 12 in placebo = The absolute change in mRSS from week 0 to week 12 in Tofacitinib.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1978</p_value>
            <method>Exact Wilcoxon</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>H0: The absolute change in mRSS from week 0 to week 24 in placebo = The absolute change in mRSS from week 0 to week 24 in Tofacitinib.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4665</p_value>
            <method>Exact Wilcoxon</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>H0: The absolute change in mRSS from week 0 to week 36 in placebo = The absolute change in mRSS from week 0 to week 36 in Tofacitinib.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.3063</p_value>
            <method>Exact Wilcoxon</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>H0: The absolute change in mRSS from week 0 to week 48 in placebo = The absolute change in mRSS from week 0 to week 48 in Tofacitinib.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.6000</p_value>
            <method>Exact Wilcoxon</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Provisional American College of Rheumatology Combined Response Index (CRISS) Systemic Sclerosis</title>
        <description>CRISS components included the following domains: modified Rodnan skin score, forced vital capacity percent predicted, Physician Global Assessment, Patient Global Assessment, and Health Assessment Questionnaire Disability-Index. An algorithm determines the predicted probability of improvement from baseline by incorporating change in the mRSS, FVC percent predicted, Physician and Patient Global Assessments, and HAQ-DI. The outcome is a continuous variable between 0.0 and 1.0 (0 - 100%). A cut-off at 0.6 in the predicted probability of being improved has yielded the smallest misclassification error. Subjects are not considered improved if, between Visit 1 and 6, they develop new: 1) renal crisis; 2) decline in FVC% predicted by 15% (relative) from baseline and confirmed after 1 month; or 3) left ventricular failure (systolic ejection fraction &lt; 45%) or pulmonary artery hypertension. Higher CRISS scores indicates improvement.</description>
        <time_frame>Week:12, 24, and 48</time_frame>
        <population>Placebo participant withdrew prior to week 24. 1 additional placebo participant and 2 tofacitinib participants withdrew prior to week 48.</population>
        <group_list>
          <group group_id="O1">
            <title>Tofacitinib Double Blind 0-24 Weeks</title>
            <description>Participants treated with an oral medication tofacitinib 5mg twice daily for 24 weeks with option to enter 24 weeks of open label tofacitinib.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Double Blind 0-24 Weeks</title>
            <description>Participants treated with an oral placebo tablet 5mg twice daily for 24 weeks with option to enter 24 weeks of open label tofacitinib.</description>
          </group>
          <group group_id="O3">
            <title>Tofacitinib to Tofacitinib Open Label 24-48 Weeks</title>
            <description>Post double blind completion, participants receive 5mg tofacitinib twice daily for 24 weeks.</description>
          </group>
          <group group_id="O4">
            <title>Placebo to Tofacitinib Open Label 24-48 Weeks</title>
            <description>Post double blind completion, participants receive 5mg tofacitinib twice daily for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Provisional American College of Rheumatology Combined Response Index (CRISS) Systemic Sclerosis</title>
          <description>CRISS components included the following domains: modified Rodnan skin score, forced vital capacity percent predicted, Physician Global Assessment, Patient Global Assessment, and Health Assessment Questionnaire Disability-Index. An algorithm determines the predicted probability of improvement from baseline by incorporating change in the mRSS, FVC percent predicted, Physician and Patient Global Assessments, and HAQ-DI. The outcome is a continuous variable between 0.0 and 1.0 (0 - 100%). A cut-off at 0.6 in the predicted probability of being improved has yielded the smallest misclassification error. Subjects are not considered improved if, between Visit 1 and 6, they develop new: 1) renal crisis; 2) decline in FVC% predicted by 15% (relative) from baseline and confirmed after 1 month; or 3) left ventricular failure (systolic ejection fraction &lt; 45%) or pulmonary artery hypertension. Higher CRISS scores indicates improvement.</description>
          <population>Placebo participant withdrew prior to week 24. 1 additional placebo participant and 2 tofacitinib participants withdrew prior to week 48.</population>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.07" lower_limit="0.005" upper_limit="0.35"/>
                    <measurement group_id="O2" value="0.02" lower_limit="0.001" upper_limit="0.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.28" lower_limit="0.001" upper_limit="1.00"/>
                    <measurement group_id="O2" value="0.09" lower_limit="0.02" upper_limit="0.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="10"/>
                    <count group_id="O4" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="0.99" lower_limit="0.33" upper_limit="1.00"/>
                    <measurement group_id="O4" value="0.83" lower_limit="0.53" upper_limit="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>H0: The CRISS score at week 12 in placebo = The CRISS score at week 12 in Tofacitinib.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4535</p_value>
            <method>Exact Wilcoxon</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>H0: The CRISS score at week 24 in placebo = The CRISS score at week 24 in Tofacitinib.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.8392</p_value>
            <method>Exact Wilcoxon</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>H0: The CRISS score at week 48 in placebo = The CRISS score at week 48 in Tofacitinib.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.9212</p_value>
            <method>Exact Wilcoxon</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>This report includes the entire time frame of the study with both Double Blind and Open Label = 48 weeks.</time_frame>
      <desc>Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.</desc>
      <group_list>
        <group group_id="E1">
          <title>Tofacitinib Double Blind 0-24 Weeks</title>
          <description>.Participants treated with an oral medication tofacitinib 5mg twice daily for 24 weeks with option to enter 24 weeks of open label tofacitinib.</description>
        </group>
        <group group_id="E2">
          <title>Placebo Double Blind 0-24 Weeks</title>
          <description>Participants treated with an oral placebo tablet 5mg twice daily for 24 weeks with option to enter 24 weeks of open label tofacitinib.</description>
        </group>
        <group group_id="E3">
          <title>Tofacitinib to Tofacitinib Open Label 24-48 Weeks</title>
          <description>Post double blind completion, participants receive 5mg tofacitinib twice daily for 24 weeks.</description>
        </group>
        <group group_id="E4">
          <title>Placebo to Tofacitinib Open Label 24-48 Weeks</title>
          <description>Post double blind completion, participants receive 5mg tofacitinib twice daily for 24 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>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="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Worsening SSc-Inpatient</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cytomegalovirus-induced Hepatitis, Drug-Induced Hepatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Bells's Palsy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetic foot ulcer (non-infection), complicated by thermal injury.</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Palpatations</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Premature Ventricular Contractions</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Increased GERD</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Colititis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Gastric Bloating</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Weight Gain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Flu-like Symptoms</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Intentional Weight Loss</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Otis Externa</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Ulcer Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Sinus Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Drug-induced hepatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Herpes Zoster</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Drug Induced Hepatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Hypercholesterolemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Hypertensive Urgency</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>&gt; 50% LDL/HDL</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Elevated Creatine Phosphokinase</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Bilateral Wrist Synovitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Joint Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Low Back Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Left Hip Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Left Knee Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Right trochanteric bursitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Cervical Myositis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Migraine</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Diziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Chronic Kidney Disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Non-obstructive Renal Calculi</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus Congestion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Pulmonary Fibrosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Muscle Weakness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Worsening ILD</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Digital Ulcer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="5" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Pruritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </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>Dinesh Khanna</name_or_title>
      <organization>University of Michigan</organization>
      <phone>734-763-7182</phone>
      <email>khannad@med.umich.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/NCT03274076
org study id: HUM00131837
nct id: NCT03274076
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This Phase I/II placebo controlled trial will evaluate tofacitinib in subjects with diffuse
      cutaneous systemic scleroderma (dcSSc). This trial is intended to provide safety, and
      tolerability data in participants with dcSSc when dosed to target exposures similar to that
      used in adult participants with rheumatoid arthritis.
The purpose of this clinical research study is to evaluate the safety, tolerability and
      efficacy of treatment with tofacitinib (study drug) versus placebo (a substance with no
      active ingredients and therefore may have no treatment benefit) in people with diffuse
      cutaneous systemic scleroderma. Subjects will be randomized to tofacitinib vs. placebo in a
      2:1 ratio at 5 mg twice a day for 24 weeks. Subjects will then be offered to participate in
      an open label phase during which they will receive tofacitinib 5 mg twice a day for 24 weeks.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Eligible subjects will be randomized to tofacitinib or placebo in a 2:1 manner.
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: The study staff (with the exception of the study pharmacist) and the patient are blinded to the treatment assignment.
measure: Number of Participants Who Experience Grade 3 or Higher Adverse Events That Occur at or Before Week 24
time frame: 24 weeks
description: Primary outcome is met if any participants experience a grade 3 or higher event prior to Week 24. A grade 3 AE would constitute as "severe". Grading was following using CTCAE v 4.03.
Note that the planned statistical analysis (Fisher's exact test) could not be performed because there were no events.
measure: Number of Grade 3 (Severe) or Higher Adverse Events That Occur Throughout the Study
time frame: Week 12, 24, 36, and 48
description: Grade 3 or higher adverse events (AEs) assessed throughout the study ( 48 weeks). A grade 3 AE would constitute as "severe". Grading was following using CTCAE v 4.03.
Note that the planned statistical analysis (calculation of rate ratio and 90% CI) could not be performed at Weeks 12 and 24 due to no events, and could not be performed at Week 36 because there were no events in the placebo group (denominator).
measure: Number of Grade 2 (Moderate) or Higher Adverse Events That Occur Throughout the Study
time frame: Week: 12, 24, 36, and 48
description: Grade 2 or higher assessed 12 weeks apart. Grade 2 AEs are determined as " moderate". Grading was performed following CTCAE v 4.03 guidance.
measure: Number of Adverse Events of Special Interest (AESI) Throughout the Study
time frame: Weeks 12, 24, 36 and 48
description: AESI are pre-defined adverse events as indicated in the protocol. They include: infections, stomach perforations, malignancy, herpes zoster and lab abnormalities.
Note that the planned statistical analysis (calculation of rate ratio and 90% CI) could not be performed at Weeks 12 and 24 because there were no events in placebo group (denominator).
measure: Change in Modified Rodnan Skin Score (mRSS)
time frame: Change from Baseline at weeks: 12, 24, 36, and 48
description: The Modified Rodnan Skin Score (mRSS) is a measure of skin thickness. Skin thickness in 17 anatomic areas was rated on a 0-3 scale and scores are summed to obtain the mRSS (range from 0 - 51), with higher mRSS scores indicating worse disease activity
measure: Provisional American College of Rheumatology Combined Response Index (CRISS) Systemic Sclerosis
time frame: Week:12, 24, and 48
description: CRISS components included the following domains: modified Rodnan skin score, forced vital capacity percent predicted, Physician Global Assessment, Patient Global Assessment, and Health Assessment Questionnaire Disability-Index. An algorithm determines the predicted probability of improvement from baseline by incorporating change in the mRSS, FVC percent predicted, Physician and Patient Global Assessments, and HAQ-DI. The outcome is a continuous variable between 0.0 and 1.0 (0 - 100%). A cut-off at 0.6 in the predicted probability of being improved has yielded the smallest misclassification error. Subjects are not considered improved if, between Visit 1 and 6, they develop new: 1) renal crisis; 2) decline in FVC% predicted by 15% (relative) from baseline and confirmed after 1 month; or 3) left ventricular failure (systolic ejection fraction < 45%) or pulmonary artery hypertension. Higher CRISS scores indicates improvement.
arm group label: Tofacitinib
arm group type: Active Comparator
description: 5mg Tofacitinib twice a day
arm group label: Placebo
arm group type: Placebo Comparator
description: 5mg Placebo twice a day
intervention type: Drug
intervention name: Tofacitinib
description: Oral medication tofacitinib 5 mg twice a day for 24 weeks.
arm group label: Tofacitinib
other name: Xeljanz
intervention type: Drug
intervention name: Placebo Oral Tablet
description: Oral Placebo 5 mg twice a day for 24 weeks
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Dinesh Khanna, MD
role: Principal Investigator
affiliation: University of Michigan
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Michigan
investigator full name: Dinesh Khanna, MD, MS
investigator title: Frederick G L Huetwell Professor of Rheumatology and Professor of Internal Medicine, Medical School
mesh term: Scleroderma, Systemic
mesh term: Scleroderma, Diffuse
mesh term: Sclerosis
mesh term: Tofacitinib
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 