<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/NCT04496960</url>
  </required_header>
  <id_info>
    <org_study_id>200131</org_study_id>
    <secondary_id>20-D-0131</secondary_id>
    <nct_id>NCT04496960</nct_id>
  </id_info>
  <brief_title>Safety of Tofacitinib, an Oral Janus Kinase Inhibitor, in Primary Sjogren's Syndrome</brief_title>
  <official_title>Safety of Tofacitinib, an Oral Janus Kinase Inhibitor, in Primary Sjogren's Syndrome; a Phase Ib-IIa Placebo-controlled Clinical Trial and Associated Mechanistic Studies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Dental and Craniofacial Research (NIDCR)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      An autoimmune disease is one in which the immune system attacks a person s own body.&#xD;
      Sjogren's syndrome (SS) is an autoimmune disease. It often involves multiple systems and&#xD;
      organs of the body. Researchers are trying to find new, more effective and safe treatments&#xD;
      for SS.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To evaluate the safety and tolerance of tofacitinib in people with SS.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      Adults ages 18-75 with SS.&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants will be screened on a separate protocol. They will undergo:&#xD;
&#xD;
        -  Medical and dental history&#xD;
&#xD;
        -  Physical exam&#xD;
&#xD;
        -  Medicine review&#xD;
&#xD;
        -  Electrocardiogram to test the heart s electrical activity (Participants will lay on a&#xD;
           table. Sticky pads will be placed on their body.)&#xD;
&#xD;
        -  Eye exam and test for dry eyes&#xD;
&#xD;
        -  Oral, head, and neck exams&#xD;
&#xD;
        -  Plaque collection (Dental plaques and tongue and mucosal scrapings will be collected&#xD;
           using a small tongue depressor.)&#xD;
&#xD;
        -  Salivary gland ultrasound&#xD;
&#xD;
        -  Blood and urine tests&#xD;
&#xD;
        -  Minor salivary gland biopsy (The lower lip will be numbed. Several tiny salivary glands&#xD;
           will be removed through a small incision.)&#xD;
&#xD;
        -  Saliva collection&#xD;
&#xD;
        -  Disease assessment.&#xD;
&#xD;
      Participants will repeat some of the screening tests during the study.&#xD;
&#xD;
      Participants will take capsules of the study drug or a placebo by mouth for 168 days.&#xD;
&#xD;
      Participants will have tests to measure blood pressure and the speed of blood flow through&#xD;
      the organs. They will also have a test that examines the function and reaction of the blood&#xD;
      vessels. For these tests, they will wear blood pressure cuffs and other sensors.&#xD;
&#xD;
      Participants will complete questionnaires about their health.&#xD;
&#xD;
      Participants will have 9 study visits over 28 weeks. They may be contacted by phone between&#xD;
      study visits.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Description:&#xD;
&#xD;
      As a primary objective, this study represents an innovative investigative measure of the&#xD;
      safety and tolerability of JAK inhibition in participants with primary Sjogren's syndrome.&#xD;
      Secondary objectives will include investigating the effects of Tofacitinib on target tissues&#xD;
      (e.g., salivary glands), systemic inflammation, and on vascular function in SS participants.&#xD;
      We also aim to identify biomarkers of response that may be useful as endpoints in future&#xD;
      studies.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      Primary Objective:&#xD;
&#xD;
      -To determine the safety and tolerability of Tofacitinib in participants with SS and mild to&#xD;
      moderate disease activity.&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
        -  To assess clinical improvement after treatment with Tofacitinib as measured by changes&#xD;
           in the European League Against Rheumatism (EULAR) Sjogren's syndrome Disease Activity&#xD;
           Index (ESSDAI) and no worsening on the Physician s Global assessment Scale (PGA).&#xD;
&#xD;
        -  To demonstrate that treatment with Tofacitinib is effective clinically and biologically&#xD;
           in SS individuals with mild to moderate disease.&#xD;
&#xD;
        -  To investigate the effects of Tofacitinib on systemic biomarkers of SS as measures&#xD;
           biological effects that can be used as outcome measures to power a larger Clinical&#xD;
           Trial.&#xD;
&#xD;
      Endpoints:&#xD;
&#xD;
      Primary Endpoint:&#xD;
&#xD;
      -Safety and tolerability will be measured by assessment of adverse events (AEs) and clinical&#xD;
      safety laboratory tests throughout the study. Toxicity is defined as any study drug-related&#xD;
      Grade 3 adverse event or higher (as measured by the National Cancer Institute (NCI), Common&#xD;
      Terminology Criteria for Adverse Events (CTCAE), Version 5.0).&#xD;
&#xD;
      Secondary Endpoints:&#xD;
&#xD;
      Preliminary assessments of clinical response will be measured by:&#xD;
&#xD;
        -  Changes in the ESSDAI score between Baseline and Day 168 (end of treatment)&#xD;
&#xD;
        -  Changes in the Physician's Global Assessment (PGA) scores between baseline and study day&#xD;
           168.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 18, 2021</start_date>
  <completion_date type="Anticipated">September 22, 2025</completion_date>
  <primary_completion_date type="Anticipated">September 21, 2025</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>safety and tolerability of tofacitinib</measure>
    <time_frame>week 24 (end of Treatment)</time_frame>
    <description>To determine the safety and tolerability of tofacitinib in subjects with SS and mild to moderate disease activity.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ESSDAI</measure>
    <time_frame>Week 24</time_frame>
    <description>The ESSDAI was developed to be used as an outcome measure in clinical trials involving Sjogren s Syndrome patient cohorts and allows for assessment/scoring of major domain activity relevant to a SS population.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>changes in salivary flow rates</measure>
    <time_frame>week 24</time_frame>
    <description>salivary flow rates are an objective measure of organ function. Low salivary flow is a primary feature of SS and may be used as a non-invasive measure of therapeutic intervention. Studying the effects of tofacitinib versus placebo via randomized trial provides the best opportunity to show causality and association.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">76</enrollment>
  <condition>Sjogren's Syndrome</condition>
  <arm_group>
    <arm_group_label>Placebo group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Receiving placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Subjects with SS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Receiving tofacidinib</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>tofacitinib</intervention_name>
    <description>XELJANZ(R) is the citrate salt of tofacitinib. Tofacitinib citrate is a white to off-white powder with the following chemical name: (3R,4R)-4-methyl-3-(methyl-7H-pyrrolo [2,3-d]pyrimidin-4-ylamino) -beta-oxo-1-piperidinepropanenitrile, 2-hydroxy-1,2,3-propanetricarboxylate (1:1) It is freely soluble in water and has a molecular weight of 504.5 Daltons. XELJANZ(R) is supplied for oral administration as 5 mg tofacitinib (equivalent to 8 mg tofacitinib citrate) white round, immediate-release film-coated tablet. Each tablet of XELJANZ(R) contains the appropriate amount of XELJANZ(R) as a citrate salt and the following inactive ingredients: microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, magnesium stearate, HPMC 2910/Hypromellose 6cP, titanium dioxide, macrogol/PEG3350, and triacetin.</description>
    <arm_group_label>Subjects with SS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>white, round, film-coated tablet</description>
    <arm_group_label>Placebo group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
        Adult primary SS participants with mild-to-moderate disease activity will be eligible for&#xD;
        this study. Enrolled participants can be na(SqrRoot) ve or failed immunosuppressive therapy&#xD;
        beyond antimalarials and glucocorticoids; to prevent bias in the cohort of participants&#xD;
        with more&#xD;
&#xD;
        recalcitrant disease. We expect that Tofacitinib is a potential second line therapy, in&#xD;
        addition to antimalarials and glucocorticoids, depending on the participant s initial&#xD;
        presentation and response. Women and members of minority groups, if eligible, will be&#xD;
        included in accordance with the NIH Policy on Inclusion of Women and Minorities as&#xD;
        Participants in Research Involving Human Participants.&#xD;
&#xD;
        In order to be eligible to participate in this study, an individual must meet all of the&#xD;
        following criteria:&#xD;
&#xD;
          1. Ability of participant to understand and the willingness to sign a written informed&#xD;
             consent document.&#xD;
&#xD;
          2. Participation and enrollment in companion protocol, 15-D-0051, Characterization of&#xD;
             Diseases with Salivary Gland Involvement.&#xD;
&#xD;
          3. Stated willingness to comply with all study procedures and availability for the&#xD;
             duration of the study&#xD;
&#xD;
          4. Male or female, aged between 18-75 years&#xD;
&#xD;
          5. In good general health as evidenced by medical history&#xD;
&#xD;
          6. Meets the 2002 American European Consensus Group classification criteria for primary&#xD;
             Sjogren's Syndrome or 2016 American College of Rheumatology/European League against&#xD;
             Rheumatism Classification Criteria (ACR-EULAR) with mild to moderate disease activity&#xD;
             defined as ESSDAI between 0 to 13 at the screening visit and &gt;0 ml/min/gland&#xD;
             stimulated saliva flow.&#xD;
&#xD;
          7. Ability to take oral medication and be willing to adhere to the study intervention&#xD;
             regimen&#xD;
&#xD;
          8. If on glucocorticoids, the dose must be less than 10 mg daily and stable for the 4&#xD;
             weeks (28 days) prior to screening visit.&#xD;
&#xD;
          9. If on hydroxychloroquine or other antimalarials such as chloroquine or quinacrine, the&#xD;
             dose must have been stable for the 12 weeks (96 days) prior to screening visit. The&#xD;
             maximum allowed dose is hydroxychloroquine up to 400 mg/day or 6.5 mg/kg/day if more&#xD;
             than 400 mg/day. The maximum allowed dose for chloroquine phosphate is up to 500 mg&#xD;
             daily and for quinacrine up to 100 mg daily.&#xD;
&#xD;
         10. Participants may be on lipid lowering medications if initiated at least 3 months prior&#xD;
             to the screening visit and dose must be stable for 4 weeks (28 days) prior to study&#xD;
             entry.&#xD;
&#xD;
         11. Males and females with potential for reproduction must agree to practice effective&#xD;
             birth control measures. Females should be on adequate contraception if they are of&#xD;
             child-bearing potential documented by a clinician, unless participants or spouse have&#xD;
             previously undergone a sterilization procedure. Adequate birth control measures are:&#xD;
             intrauterine device (IUD) alone or hormone implants, hormone patches, injectable, or&#xD;
             oral contraceptives plus a barrier method (male condom, female condom or diaphragm),&#xD;
             abstinence or a vasectomized partner.&#xD;
&#xD;
         12. Agreement to adhere to Lifestyle Considerations (see section 5.4) throughout study&#xD;
             duration&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
        In order to be eligible to participate in this study, an individual must not meet any of&#xD;
        the following criteria:&#xD;
&#xD;
          1. Current or prior treatment with rituximab, belimumab or any other biologic agent in&#xD;
             the 6 months prior to screening.&#xD;
&#xD;
          2. Current treatment with methotrexate, azathioprine, mycophenolate mofetil,&#xD;
             cyclosporine, tacrolimus, or other less common immunomodulatory drugs such as those&#xD;
             falling into the class of disease-modifying antirheumatic drugs (DMARDs), not&#xD;
             otherwise specified herein. Participants previously on methotrexate, azathioprine,&#xD;
             mycophenolate mofetil, cyclosporine or tacrolimus, or other DMARDs should have&#xD;
             withdrawn drug for at least 8 weeks (56 days) at the time of screening.&#xD;
&#xD;
          3. Treatment with cyclophosphamide, pulse methylprednisolone or IVIG within 6 months&#xD;
             prior to screening.&#xD;
&#xD;
          4. Current treatment with potent inhibitors of Cytochrome P450 3A4 (CYP3A4) (e.g.,&#xD;
             ketoconazole) or receiving one or more concomitant medications that result in both&#xD;
             moderate inhibition of CYP3A4 and potent inhibition of CYP2C19 (e.g., fluconazole)&#xD;
             that would increase serum availability of Tofacitinib. Past treatment with the&#xD;
             aforementioned agent is allowed if it was more than a week prior to the administration&#xD;
             of the first dose of study medication.&#xD;
&#xD;
          5. History of chronic liver disease, not including well-controlled Sjogren s-related&#xD;
             chronic liver disease or elevated LFTs:&#xD;
&#xD;
               -  ALT or AST &gt;= 2x upper limit of normal at screening&#xD;
&#xD;
               -  Serum unconjugated bilirubin &gt; 2mg/dL at screening&#xD;
&#xD;
          6. Serum creatinine &gt;1.5mg/dL.&#xD;
&#xD;
          7. Protein to creatinine ratio of more than 1mg/dL at screening (repeated and confirmed&#xD;
             three times or confirmed with 24 hours urine protein of more than 1000mg).&#xD;
&#xD;
          8. Active urinary sediment (WBC, RBC or mixed cellular casts 1+ or more /hpf).&#xD;
&#xD;
          9. Hypercholesterolemia: Values after 8-12 hour fasting blood specimen: total cholesterol&#xD;
             &gt;250 mg/dL or LDL &gt;180 mg/dL or hypertriglyceridemia (triglyceride &gt;300 mg/dL)&#xD;
             within-45 days of screening visit.&#xD;
&#xD;
         10. WBC &lt;2500/microliter or ANC &lt;1,000/microliter, Hgb &lt;9.0 g/dL or platelets&#xD;
             &lt;70,000/microliter or absolute lymphocyte count &lt; 500/microliter.&#xD;
&#xD;
         11. Pregnant or lactating women. Women of childbearing potential are required to have a&#xD;
             negative pregnancy test at screening.&#xD;
&#xD;
         12. A history of drug or alcohol abuse within the 6 months prior to screening.&#xD;
&#xD;
         13. Currently receiving hemodialysis, peritoneal dialysis, or intestinal dialysis.&#xD;
&#xD;
         14. Active infection that requires the use of oral or intravenous antibiotics unresolved&#xD;
             at least 14 days prior to the administration of the first dose of study medication.&#xD;
&#xD;
         15. Active chronic infections including but not limited to HIV, Hepatitis B, Hepatitis C,&#xD;
             and BK viremia at screening visit.&#xD;
&#xD;
         16. Current or previous diagnosis of malignant disease, except for basal cell or squamous&#xD;
             cell carcinoma of the skin with complete excision and clear borders or adequately&#xD;
             treated in situ carcinoma of the cervix.&#xD;
&#xD;
         17. Known active tuberculosis. Participants with treated latent tuberculosis (LTB) will be&#xD;
             eligible to participate. Participants with untreated LTB will not be excluded but will&#xD;
             be evaluated by an infectious disease (I.D.) consultant and may become eligible for&#xD;
             trial based on infectious disease consultant recommendations.&#xD;
&#xD;
         18. History of opportunistic infections.&#xD;
&#xD;
         19. Participants with active renal or central nervous system disease or a high activity&#xD;
             level in any organ system (except articular) in ESSDAI^54.&#xD;
&#xD;
         20. Participants with known increased risk factors for major adverse cardiac event (MACE)&#xD;
             including a history of:&#xD;
&#xD;
               -  Ischemic heart disease (e.g., history of acute myocardial infarction)&#xD;
&#xD;
               -  Heart failure&#xD;
&#xD;
               -  Cardiomyopathy&#xD;
&#xD;
               -  Severe valvular heart disease&#xD;
&#xD;
               -  Significant arrhythmias&#xD;
&#xD;
               -  Chronic renal failure&#xD;
&#xD;
               -  Cerebrovascular accident or transient ischemic attack&#xD;
&#xD;
               -  Uncontrolled diabetes mellitus&#xD;
&#xD;
               -  Uncontrolled hypertension&#xD;
&#xD;
               -  Current smokers or former smokers with less than 3 years since complete cessation&#xD;
                  and/or &gt;20 pack-years of smoking history.&#xD;
&#xD;
         21. Significant impairment of major organ function (lung, heart, liver, kidney) or any&#xD;
             condition that, in the opinion of the Investigator, would jeopardize the participant s&#xD;
             safety following exposure to the study drug.&#xD;
&#xD;
         22. Known history of arterial or venous thrombosis or at high risk for clotting disorder&#xD;
&#xD;
         23. Psychiatric illness or history of medical non-compliance that the study team feels&#xD;
             will make the patient unlikely to complete the study&#xD;
&#xD;
         24. Uncontrolled thyroid disease as per PI or medically responsible investigator.&#xD;
&#xD;
         25. Known allergic reactions to Tofacitinib or its components&#xD;
&#xD;
         26. Treatment with another investigational drug/intervention within six months except for&#xD;
             COVID-19 vaccines or therapies that have been granted an FDA emergency authorization.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Blake M Warner, D.D.S.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Dental and Craniofacial Research (NIDCR)</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sasha D Clary</last_name>
    <phone>(301) 827-5031</phone>
    <email>sasha.clary@nih.gov</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Blake M Warner, D.D.S.</last_name>
    <phone>(301) 500-8063</phone>
    <email>blake.warner@nih.gov</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)</last_name>
      <phone>800-411-1222</phone>
      <phone_ext>TTY8664111010</phone_ext>
      <email>prpl@cc.nih.gov</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2020-D-0131.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <verification_date>September 8, 2023</verification_date>
  <study_first_submitted>August 2, 2020</study_first_submitted>
  <study_first_submitted_qc>August 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2020</study_first_posted>
  <last_update_submitted>September 12, 2023</last_update_submitted>
  <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Salivary</keyword>
  <keyword>Dry Mouth</keyword>
  <keyword>Safety</keyword>
  <keyword>Inflammation</keyword>
  <keyword>Xerostomia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sjogren's Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tofacitinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>.The Study team does not have a plan or not yet known if there is a plan to make IPD available.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04496960
org study id: 200131
secondary id: 20-D-0131
nct id: NCT04496960
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
Background:

      An autoimmune disease is one in which the immune system attacks a person s own body.
      Sjogren's syndrome (SS) is an autoimmune disease. It often involves multiple systems and
      organs of the body. Researchers are trying to find new, more effective and safe treatments
      for SS.

      Objective:

      To evaluate the safety and tolerance of tofacitinib in people with SS.

      Eligibility:

      Adults ages 18-75 with SS.

      Design:

      Participants will be screened on a separate protocol. They will undergo:

        -  Medical and dental history

        -  Physical exam

        -  Medicine review

        -  Electrocardiogram to test the heart s electrical activity (Participants will lay on a
           table. Sticky pads will be placed on their body.)

        -  Eye exam and test for dry eyes

        -  Oral, head, and neck exams

        -  Plaque collection (Dental plaques and tongue and mucosal scrapings will be collected
           using a small tongue depressor.)

        -  Salivary gland ultrasound

        -  Blood and urine tests

        -  Minor salivary gland biopsy (The lower lip will be numbed. Several tiny salivary glands
           will be removed through a small incision.)

        -  Saliva collection

        -  Disease assessment.

      Participants will repeat some of the screening tests during the study.

      Participants will take capsules of the study drug or a placebo by mouth for 168 days.

      Participants will have tests to measure blood pressure and the speed of blood flow through
      the organs. They will also have a test that examines the function and reaction of the blood
      vessels. For these tests, they will wear blood pressure cuffs and other sensors.

      Participants will complete questionnaires about their health.

      Participants will have 9 study visits over 28 weeks. They may be contacted by phone between
      study visits.
Study Description:

      As a primary objective, this study represents an innovative investigative measure of the
      safety and tolerability of JAK inhibition in participants with primary Sjogren's syndrome.
      Secondary objectives will include investigating the effects of Tofacitinib on target tissues
      (e.g., salivary glands), systemic inflammation, and on vascular function in SS participants.
      We also aim to identify biomarkers of response that may be useful as endpoints in future
      studies.

      Objectives:

      Primary Objective:

      -To determine the safety and tolerability of Tofacitinib in participants with SS and mild to
      moderate disease activity.

      Secondary Objectives:

        -  To assess clinical improvement after treatment with Tofacitinib as measured by changes
           in the European League Against Rheumatism (EULAR) Sjogren's syndrome Disease Activity
           Index (ESSDAI) and no worsening on the Physician s Global assessment Scale (PGA).

        -  To demonstrate that treatment with Tofacitinib is effective clinically and biologically
           in SS individuals with mild to moderate disease.

        -  To investigate the effects of Tofacitinib on systemic biomarkers of SS as measures
           biological effects that can be used as outcome measures to power a larger Clinical
           Trial.

      Endpoints:

      Primary Endpoint:

      -Safety and tolerability will be measured by assessment of adverse events (AEs) and clinical
      safety laboratory tests throughout the study. Toxicity is defined as any study drug-related
      Grade 3 adverse event or higher (as measured by the National Cancer Institute (NCI), Common
      Terminology Criteria for Adverse Events (CTCAE), Version 5.0).

      Secondary Endpoints:

      Preliminary assessments of clinical response will be measured by:

        -  Changes in the ESSDAI score between Baseline and Day 168 (end of treatment)

        -  Changes in the Physician's Global Assessment (PGA) scores between baseline and study day
           168.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: safety and tolerability of tofacitinib
time frame: week 24 (end of Treatment)
description: To determine the safety and tolerability of tofacitinib in subjects with SS and mild to moderate disease activity.
measure: ESSDAI
time frame: Week 24
description: The ESSDAI was developed to be used as an outcome measure in clinical trials involving Sjogren s Syndrome patient cohorts and allows for assessment/scoring of major domain activity relevant to a SS population.
measure: changes in salivary flow rates
time frame: week 24
description: salivary flow rates are an objective measure of organ function. Low salivary flow is a primary feature of SS and may be used as a non-invasive measure of therapeutic intervention. Studying the effects of tofacitinib versus placebo via randomized trial provides the best opportunity to show causality and association.
arm group label: Placebo group
arm group type: Placebo Comparator
description: Receiving placebo
arm group label: Subjects with SS
arm group type: Experimental
description: Receiving tofacidinib
intervention type: Drug
intervention name: tofacitinib
description: XELJANZ(R) is the citrate salt of tofacitinib. Tofacitinib citrate is a white to off-white powder with the following chemical name: (3R,4R)-4-methyl-3-(methyl-7H-pyrrolo [2,3-d]pyrimidin-4-ylamino) -beta-oxo-1-piperidinepropanenitrile, 2-hydroxy-1,2,3-propanetricarboxylate (1:1) It is freely soluble in water and has a molecular weight of 504.5 Daltons. XELJANZ(R) is supplied for oral administration as 5 mg tofacitinib (equivalent to 8 mg tofacitinib citrate) white round, immediate-release film-coated tablet. Each tablet of XELJANZ(R) contains the appropriate amount of XELJANZ(R) as a citrate salt and the following inactive ingredients: microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, magnesium stearate, HPMC 2910/Hypromellose 6cP, titanium dioxide, macrogol/PEG3350, and triacetin.
arm group label: Subjects with SS
intervention type: Other
intervention name: Placebo
description: white, round, film-coated tablet
arm group label: Placebo group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Blake M Warner, D.D.S.
role: Principal Investigator
affiliation: National Institute of Dental and Craniofacial Research (NIDCR)
last name: Sasha D Clary
phone: (301) 827-5031
email: sasha.clary@nih.gov
last name: Blake M Warner, D.D.S.
phone: (301) 500-8063
email: blake.warner@nih.gov
facility: 
status: Recruiting
contact: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2020-D-0131.html
description: NIH Clinical Center Detailed Web Page
responsible party type: Sponsor
mesh term: Sjogren's Syndrome
mesh term: Syndrome
mesh term: Tofacitinib
sharing ipd: Undecided
ipd description: .The Study team does not have a plan or not yet known if there is a plan to make IPD available.