<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/NCT03026504</url>
  </required_header>
  <id_info>
    <org_study_id>16-008993</org_study_id>
    <nct_id>NCT03026504</nct_id>
  </id_info>
  <brief_title>Baricitinib in Relapsing Giant Cell Arteritis</brief_title>
  <official_title>Baricitinib in Relapsing Giant Cell Arteritis (GCA): A Phase II, Single-institution, Open-label Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Matthew J Koster</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eli Lilly and Company</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate the safety and effectiveness of baricitinib in the treatment of&#xD;
      giant cell arteritis. All participants will be taking prednisone at the start of the study.&#xD;
      The prednisone will be reduced according to a standardized tapering schedule while&#xD;
      participants continue to take one tablet of baricitinib daily for 52 weeks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Baricitinib, an orally administered, potent, selective and reversible inhibitor of JAK1 and&#xD;
      JAK2 has shown preliminary safety and efficacy in chronic, immune-mediated inflammatory&#xD;
      conditions such as rheumatoid arthritis and psoriasis. This small molecule is uniquely suited&#xD;
      as a potential novel therapeutic agent in GCA because of its suppressive effect on both the&#xD;
      Th17 (IL-6, IL-23) andTh1 (IL-12, IFN-γ) pathways.&#xD;
&#xD;
      This study will evaluate the safety and tolerability of baricitinib in a population of&#xD;
      patients with relapsing GCA. The study is an open-label pilot study assessing the safety and&#xD;
      tolerability of baricitinib (4 mg daily, oral, for 52 weeks) in addition to a standardized&#xD;
      glucocorticoid taper. It is anticipated that adjunct baricitinib will be safe and well&#xD;
      tolerated by patients with GCA and demonstrate preliminary efficacy as measured by reducing&#xD;
      inflammatory markers, decreasing steroid requirements and increasing relapse-free survival.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 9, 2017</start_date>
  <completion_date type="Actual">April 12, 2021</completion_date>
  <primary_completion_date type="Actual">April 12, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>52 weeks</time_frame>
    <description>The percentage of subjects who experienced greater than or equal to one adverse event</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Giant Cell Arteritis (GCA) Relapse</measure>
    <time_frame>24 weeks, 52 weeks</time_frame>
    <description>The number of subjects to experience relapse of GCA at 24 weeks and 52 weeks. As defined as:&#xD;
Presence of ESR ≥30 mm/hour and/or CRP ≥10 mg/L and the presence of at least one of the following:&#xD;
Unequivocal cranial symptoms of GCA.&#xD;
Unequivocal symptoms of PMR.&#xD;
Other features judged by the clinician to be consistent with GCA or PMR (eg, fever of unknown origin, unexplained weight loss, fatigue/ malaise, etc) for which no other aetiology was identified as causational.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Erythrocyte Sedimentation Rate (ESR)</measure>
    <time_frame>week 0, week 24, week 52</time_frame>
    <description>ESR is a blood test that detects and monitors inflammation in the body. The normal range is 0 to 22 mm/hr for men and 0 to 29 mm/hr for women.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C Reactive Protein (CRP)</measure>
    <time_frame>week 0, week 24, week 52</time_frame>
    <description>C-reactive protein is a substance produced by the liver in response to inflammation. Normal blood CRP levels are below 3.0 mg/L.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Arteritis, Giant Cell</condition>
  <arm_group>
    <arm_group_label>Baricitinib Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 milligrams oral Baricitinib daily for 52 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Baricitinib</intervention_name>
    <description>4 milligrams oral Baricitinib daily for 52 weeks</description>
    <arm_group_label>Baricitinib Therapy</arm_group_label>
    <other_name>JAK2 Inhibitor</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Diagnosis of Giant Cell Arteritis (GCA) defined by the following Revised GCA Diagnosis&#xD;
             Criteria:&#xD;
&#xD;
               -  Age ≥50 years.&#xD;
&#xD;
               -  History of Erythrocyte Sedimentation Rate (ESR) ≥ 50 mm/hour or C-Reactive&#xD;
                  Protein (CRP) ≥ 10 mg/L.&#xD;
&#xD;
               -  Presence of at least one of the following:&#xD;
&#xD;
                    -  Unequivocal cranial symptoms of GCA (new onset localized headache, scalp or&#xD;
                       temporal artery tenderness, otherwise unexplained mouth or jaw pain upon&#xD;
                       mastication).&#xD;
&#xD;
                    -  Unequivocal symptoms of Polymyalgia Rheumatica (PMR), defined as shoulder&#xD;
                       and/or hip girdle pain associated with inflammatory stiffness.&#xD;
&#xD;
                    -  Systemic inflammatory disease in which the presence of the fever (&gt;38&#xD;
                       degrees Celsius for ≥ 7 days), weight loss (&gt; 5 pounds or 10% premorbid&#xD;
                       weight), and/or night sweats were attributable to GCA and no other cause was&#xD;
                       identified.&#xD;
&#xD;
               -  Presence of at least one of the following:&#xD;
&#xD;
                    -  Temporal artery biopsy revealing features of GCA.&#xD;
&#xD;
                    -  Evidence of large-vessel vasculitis by angiography or cross-sectional&#xD;
                       imaging, including but not limited to magnetic resonance angiography (MRA),&#xD;
                       computed tomography angiography (CTA), positron emission tomography-computed&#xD;
                       tomography (PET-CT) or evidence of large-vessel or temporal artery&#xD;
                       vasculitis by ultrasound (US).&#xD;
&#xD;
          2. Relapse with active GCA within 6 weeks of study entry where active disease is defined&#xD;
             by an ESR ≥30 mm/hr or CRP ≥10 mg/L AND the presence of at least one of the following:&#xD;
&#xD;
               -  Unequivocal cranial symptoms of GCA (new onset or recurrent localized headache,&#xD;
                  scalp or temporal artery tenderness, otherwise unexplained mouth or jaw pain upon&#xD;
                  mastication [i.e., jaw claudication]).&#xD;
&#xD;
               -  Unequivocal symptoms of PMR, defined as shoulder and/or hip girdle pain&#xD;
                  associated with inflammatory stiffness.&#xD;
&#xD;
               -  Other feature(s) judged by the clinician investigator to be consistent with GCA&#xD;
                  or PMR flares (e.g. fever of unknown origin, weight loss, fatigue/malaise, etc.)&#xD;
&#xD;
          3. Clinically stable at baseline visit (study drug initiation) such that the subject is&#xD;
             able to safely participate in the standardized taper regimen in the opinion of the&#xD;
             investigator.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Presence of any other autoimmune disease (such as systemic lupus erythematosus,&#xD;
             rheumatoid arthritis, inflammatory arthritis, other vasculitides, scleroderma,&#xD;
             polymyositis, dermatomyositis, or other similar systemic connective tissue diseases).&#xD;
&#xD;
          2. Subjects demonstrating symptoms of visual loss (transient or permanent blindness) or&#xD;
             diplopia attributable to GCA.&#xD;
&#xD;
          3. Subjects with history of aortic dissection, myocardial infarction, or cerebrovascular&#xD;
             attack attributable to GCA.&#xD;
&#xD;
          4. Has received, or is expected to receive, any live virus vaccinations (with the&#xD;
             exception of herpes zoster vaccination) within 3 months before the first dose of study&#xD;
             drug, during the study, or within 3 months after the last administration of the study&#xD;
             drug. All patients who have not received the herpes zoster vaccine at screening will&#xD;
             be encouraged (per local guidelines) to do so prior to randomization; vaccination must&#xD;
             occur &gt;4 weeks prior to randomization and start of investigational product. Patients&#xD;
             will be excluded if they were exposed to herpes zoster vaccination within 4 weeks of&#xD;
             planned randomization.&#xD;
&#xD;
          5. Organ transplant recipients.&#xD;
&#xD;
          6. Have had a major surgery within 8 weeks prior to screening or will require major&#xD;
             surgery during the study that, in the opinion of the investigator would pose an&#xD;
             unacceptable risk to the patient.&#xD;
&#xD;
          7. Have experienced any of the following within 12 weeks of screening: myocardial&#xD;
             infarction (MI), unstable ischemic heart disease, stroke, or New York Heart&#xD;
             Association Stage IV heart failure&#xD;
&#xD;
          8. Have a history or presence of cardiovascular (including but not limited to&#xD;
             uncontrolled hypertension), respiratory, hepatic, gastrointestinal, endocrine,&#xD;
             hematological, neurological, or neuropsychiatric disorders, or any other serious&#xD;
             and/or unstable illness that, in the opinion of the investigator, could constitute an&#xD;
             unacceptable risk when taking investigational product or interfere with the&#xD;
             interpretation of data.&#xD;
&#xD;
          9. Are largely or wholly incapacitated permitting little or no self-care, such as being&#xD;
             bedridden or confined to a wheelchair.&#xD;
&#xD;
         10. Have an estimated glomerular filtration rate (eGFR) of &lt;50 mL/min/1.73 m^².&#xD;
&#xD;
         11. Have a history of chronic liver disease with the most recent available aspartate&#xD;
             aminotransferase (AST) or alanine aminotransferase (ALT) &gt; 2 times the upper limit of&#xD;
             normal (ULN) or the most recent available total bilirubin ≥1.5 times ULN (if&#xD;
             available).&#xD;
&#xD;
         12. Have a history of lymphoproliferative disease; or have signs or symptoms suggestive of&#xD;
             possible lymphoproliferative disease, including lymphadenopathy or splenomegaly; or&#xD;
             have active primary or recurrent malignant disease; or have been in remission from&#xD;
             clinically significant malignancy for &lt; 5 years.&#xD;
&#xD;
               1. Subjects with uterine cervical carcinoma in situ that has been resected with no&#xD;
                  evidence of recurrence or metastatic disease for at least 3 years may participate&#xD;
                  in the study&#xD;
&#xD;
               2. Subjects with basal cell or squamous epithelial skin cancers which have been&#xD;
                  completely resected with no evidence of recurrence for at least 3 years may&#xD;
                  participate in the study.&#xD;
&#xD;
         13. Active infections, or history of recurrent infections or have required management of&#xD;
             acute or chronic infections as evidenced by any of the following:&#xD;
&#xD;
               1. Currently on any suppressive therapy for a chronic infection (such as&#xD;
                  tuberculosis, cytomegalovirus, herpes simplex, herpes zoster, or atypical&#xD;
                  mycobacteria).&#xD;
&#xD;
               2. History or suspicion of chronic infection (e.g. prosthetic joint infection)&#xD;
&#xD;
               3. Hospitalization for treatment of infection within 60 days of baseline visit&#xD;
&#xD;
               4. Use of parenteral (IV or IM) antimicrobials (antibacterial, antifungals,&#xD;
                  antivirals, or antiparasitic agents) within 60 days of baseline or oral&#xD;
                  antimicrobials within 30 days of baseline visit for treatment of an active&#xD;
                  infection. This does not include the use of antibiotics for prophylaxis against&#xD;
                  pneumocystis pneumonia since this is considered standard of care for patients on&#xD;
                  prednisone ≥ 20 mg/day for longer than 3 consecutive months.&#xD;
&#xD;
         14. Have had symptomatic herpes zoster infection within 12 weeks prior to screening.&#xD;
&#xD;
         15. Have a history of disseminated/complicated herpes zoster [for example, multidermatomal&#xD;
             involvement, ophthalmic zoster or Central Nervous System (CNS) involvement]&#xD;
&#xD;
         16. In the opinion of the investigator, are at an unacceptable risk for participating in&#xD;
             the study.&#xD;
&#xD;
         17. Have known or documented diagnosis of human immunodeficiency virus (HIV).&#xD;
&#xD;
         18. Have known or documented primary immunodeficiency.&#xD;
&#xD;
         19. Have had household contact with a person with active tuberculosis (TB) and did not&#xD;
             receive appropriate and documented prophylaxis for TB.&#xD;
&#xD;
         20. Have had evidence of active TB or have previously had evidence of active TB and did&#xD;
             not receive appropriate and documented treatment.&#xD;
&#xD;
         21. Have evidence of latent TB as documented by a local lab positive QuantiFERON®-TB Gold&#xD;
             test and a normal chest x-ray, unless a patient completes at least 4 weeks of&#xD;
             appropriate treatment prior to study entry and agrees to complete the remainder of&#xD;
             treatment while in the trial.&#xD;
&#xD;
               1. If the QuantiFERON®-TB Gold test results are positive, the patient will be&#xD;
                  considered to have latent TB and will be excluded. If the test is indeterminate,&#xD;
                  the test may be repeated once within 2 weeks of the initial value. If the repeat&#xD;
                  test results are again not negative, the subject will be considered to have&#xD;
                  latent TB (for purposes of this study) and will be excluded.&#xD;
&#xD;
               2. Exceptions include subjects with a history of active or latent TB who have&#xD;
                  documented evidence of appropriate treatment and with no history of re-exposure&#xD;
                  since their treatment was completed. (Such subjects would not be required to&#xD;
                  undergo the protocol specific TB testing, but would require a baseline chest&#xD;
                  x-ray).&#xD;
&#xD;
         22. Have a positive test for Hepatitis B Virus (HBV) defined as:&#xD;
&#xD;
               1. Positive for hepatitis B surface antigen (HBsAg), or&#xD;
&#xD;
               2. Positive for anti-hepatitis B core antibody (HBcAb) If any of the Hepatitis B&#xD;
                  tests have an indeterminate result, confirmatory testing will be performed by an&#xD;
                  alternate method.&#xD;
&#xD;
         23. Have Hepatitis C Virus (HCV) (positive for anti-hepatitis C antibody with confirmed&#xD;
             presence of HCV).&#xD;
&#xD;
         24. Have any of the following specific abnormalities on screening tests:&#xD;
&#xD;
               1. ALT or AST &gt; 2 x ULN&#xD;
&#xD;
               2. Total bilirubin ≥1.5 x ULN&#xD;
&#xD;
               3. Hemoglobin &lt; 10 grams/deciliter&#xD;
&#xD;
               4. Total white blood cell count (WBC) &lt; 2500 cells/μL)&#xD;
&#xD;
               5. Neutropenia (absolute neutrophil count [ANC] &lt; 1200 cells/μL&#xD;
&#xD;
               6. Lymphopenia (lymphocyte count &lt; 750 cells/μL)&#xD;
&#xD;
               7. Thrombocytopenia (platelets &lt; 100,000 cells/μL)&#xD;
&#xD;
               8. eGFR &lt; 50 mL/min/1.73m²&#xD;
&#xD;
             In the case of any of the aforementioned laboratory abnormalities, the tests may be&#xD;
             repeated once within approximately 2 weeks from the initial values, and values&#xD;
             resulting from repeat testing may be accepted for enrollment eligibility if they meet&#xD;
             the eligibility criterion.&#xD;
&#xD;
         25. Are pregnant or breast feeding at the time of screening or enrollment.&#xD;
&#xD;
         26. Are females of childbearing potential who do not agree to use 2 forms of highly&#xD;
             effective birth control when engaging in sexual intercourse with a male partner while&#xD;
             enrolled in the study and for at least 4 weeks following the last dose of the study&#xD;
             drug&#xD;
&#xD;
               1. Females of non-childbearing potential are defined as women ≥60 years of age,&#xD;
                  women&#xD;
&#xD;
                  ≥40 but &lt;60 years of age what had had cessation of menses for at least 12 months,&#xD;
                  or whom who are congenitally or surgically sterile (that is have had a&#xD;
                  hysterectomy, or bilateral oophorectomy or tubal ligation)&#xD;
&#xD;
               2. The following birth control methods are considered highly effective (the subject&#xD;
                  should choose 2 to be used with their male partner&#xD;
&#xD;
             i. Oral, injectable, or implanted hormonal contraceptives ii. Condom with spermicidal&#xD;
             foam, gel film, cream or suppository iii. Occlusive cap (diaphragm or cervical/vault&#xD;
             caps) with a spermicidal foam, gel, film, cream or suppository iv. . Intrauterine&#xD;
             device v. Intrauterine system (for example progestin-releasing coil) vi. Vasectomies&#xD;
             male (with appropriate post-vasectomy documentation of the absence of sperm in the&#xD;
             ejaculate)&#xD;
&#xD;
         27. Are males who do not agree to use 2 forms of highly effective birth control (see&#xD;
             above) while engaging in sexual intercourse with females partners of childbearing&#xD;
             potential while enrolled in the study and for 4 weeks after the last dose of the study&#xD;
             drug.&#xD;
&#xD;
         28. Have donated more than a single unit of blood within 4 weeks prior to screening or&#xD;
             intend to donate blood during the course of the study.&#xD;
&#xD;
         29. Have a history of chronic alcohol abuse, IV drug abuse, or other illicit drug above&#xD;
             within the 2 years prior to screening.&#xD;
&#xD;
         30. Have previously received baricitinib for other investigational study.&#xD;
&#xD;
         31. Are unable or unwilling to make themselves available for the duration of the study&#xD;
             and/or are unwilling to follow study restrictions/procedures&#xD;
&#xD;
         32. Are currently enrolled in, or discontinued within 4 weeks prior to screening from any&#xD;
             other clinical trial involving an investigational product or nonapproved use of a drug&#xD;
             or device or concurrently enrolled in any other type of medical research judged not to&#xD;
             be scientifically or medically compatible with this study.&#xD;
&#xD;
         33. Are investigator site personnel directly affiliated with this study and/or their&#xD;
             immediate families. Immediate family is defined as a spouse, parent, child, or sibling&#xD;
             whether biological or legally adopted.&#xD;
&#xD;
         34. Have a chronic medical illness requiring the use of oral of IV glucocorticoid&#xD;
             treatment (e.g. asthma or emphysema) during the trial or requiring long term&#xD;
             glucocorticoid treatment such that they would not be able to safely undergone a&#xD;
             standardized glucocorticoid taper.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kenneth Warrington, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>January 17, 2017</study_first_submitted>
  <study_first_submitted_qc>January 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 20, 2017</study_first_posted>
  <results_first_submitted>March 15, 2022</results_first_submitted>
  <results_first_submitted_qc>April 7, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">April 8, 2022</results_first_posted>
  <last_update_submitted>April 7, 2022</last_update_submitted>
  <last_update_submitted_qc>April 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Matthew J Koster</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polymyalgia Rheumatica</mesh_term>
    <mesh_term>Giant Cell Arteritis</mesh_term>
    <mesh_term>Arteritis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 30, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/04/NCT03026504/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Single Arm</title>
          <description>All participants assigned to baricitinib 4 mg daily orally for 52 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Baricitinib Therapy</title>
          <description>4 milligrams oral Baricitinib daily for 52 weeks&#xD;
Baricitinib: 4 milligrams oral Baricitinib daily for 52 weeks</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" 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="72.4" spread="7.2"/>
                  </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="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>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_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Duration of GCA</title>
          <units>months</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9" lower_limit="7" upper_limit="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26.3" spread="3.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Median number of prior GCA relapses</title>
          <units>events</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1" lower_limit="1" upper_limit="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline Predinose dose</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>30 mg/day</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20 mg/day</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>10 mg/day</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Adverse Events</title>
        <description>The percentage of subjects who experienced greater than or equal to one adverse event</description>
        <time_frame>52 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Baricitinib Therapy</title>
            <description>4 milligrams oral Baricitinib daily for 52 weeks&#xD;
Baricitinib: 4 milligrams oral Baricitinib daily for 52 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Adverse Events</title>
          <description>The percentage of subjects who experienced greater than or equal to one adverse event</description>
          <units>percentage of subjects</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Giant Cell Arteritis (GCA) Relapse</title>
        <description>The number of subjects to experience relapse of GCA at 24 weeks and 52 weeks. As defined as:&#xD;
Presence of ESR ≥30 mm/hour and/or CRP ≥10 mg/L and the presence of at least one of the following:&#xD;
Unequivocal cranial symptoms of GCA.&#xD;
Unequivocal symptoms of PMR.&#xD;
Other features judged by the clinician to be consistent with GCA or PMR (eg, fever of unknown origin, unexplained weight loss, fatigue/ malaise, etc) for which no other aetiology was identified as causational.</description>
        <time_frame>24 weeks, 52 weeks</time_frame>
        <population>One subject withdrawn at week 8. Data was not collected or analyzed for week 24 and week 52</population>
        <group_list>
          <group group_id="O1">
            <title>Baricitinib Therapy</title>
            <description>4 milligrams oral Baricitinib daily for 52 weeks&#xD;
Baricitinib: 4 milligrams oral Baricitinib daily for 52 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Giant Cell Arteritis (GCA) Relapse</title>
          <description>The number of subjects to experience relapse of GCA at 24 weeks and 52 weeks. As defined as:&#xD;
Presence of ESR ≥30 mm/hour and/or CRP ≥10 mg/L and the presence of at least one of the following:&#xD;
Unequivocal cranial symptoms of GCA.&#xD;
Unequivocal symptoms of PMR.&#xD;
Other features judged by the clinician to be consistent with GCA or PMR (eg, fever of unknown origin, unexplained weight loss, fatigue/ malaise, etc) for which no other aetiology was identified as causational.</description>
          <population>One subject withdrawn at week 8. Data was not collected or analyzed for week 24 and week 52</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="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>24 Weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>52 Weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Erythrocyte Sedimentation Rate (ESR)</title>
        <description>ESR is a blood test that detects and monitors inflammation in the body. The normal range is 0 to 22 mm/hr for men and 0 to 29 mm/hr for women.</description>
        <time_frame>week 0, week 24, week 52</time_frame>
        <population>One subject withdrawn at week 8. Data was not collected or analyzed for week 24 and week 52</population>
        <group_list>
          <group group_id="O1">
            <title>Baricitinib Therapy</title>
            <description>4 milligrams oral Baricitinib daily for 52 weeks&#xD;
Baricitinib: 4 milligrams oral Baricitinib daily for 52 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Erythrocyte Sedimentation Rate (ESR)</title>
          <description>ESR is a blood test that detects and monitors inflammation in the body. The normal range is 0 to 22 mm/hr for men and 0 to 29 mm/hr for women.</description>
          <population>One subject withdrawn at week 8. Data was not collected or analyzed for week 24 and week 52</population>
          <units>mm/hr</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="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7" lower_limit="6" upper_limit="17"/>
                  </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="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13" lower_limit="7" upper_limit="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10" lower_limit="5" upper_limit="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>C Reactive Protein (CRP)</title>
        <description>C-reactive protein is a substance produced by the liver in response to inflammation. Normal blood CRP levels are below 3.0 mg/L.</description>
        <time_frame>week 0, week 24, week 52</time_frame>
        <population>One subject withdrawn at week 8. Data was not collected or analyzed for week 24 and week 52. NA indicates CRP levels are &lt; 3 mg/L, but lab values do not return any actual values that are below this level of detection. Unable to use the &quot;&lt;&quot; symbol.</population>
        <group_list>
          <group group_id="O1">
            <title>Baricitinib Therapy</title>
            <description>4 milligrams oral Baricitinib daily for 52 weeks&#xD;
Baricitinib: 4 milligrams oral Baricitinib daily for 52 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>C Reactive Protein (CRP)</title>
          <description>C-reactive protein is a substance produced by the liver in response to inflammation. Normal blood CRP levels are below 3.0 mg/L.</description>
          <population>One subject withdrawn at week 8. Data was not collected or analyzed for week 24 and week 52. NA indicates CRP levels are &lt; 3 mg/L, but lab values do not return any actual values that are below this level of detection. Unable to use the &quot;&lt;&quot; symbol.</population>
          <units>mg/L</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="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.4" lower_limit="NA" upper_limit="6.9">N/A indicates CRP levels are &lt; 3 mg/L, but lab values do not return any actual values that are below this level of detection. Unable to use the &quot;&lt;&quot; symbol.</measurement>
                  </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="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">N/A indicates CRP levels are &lt; 3 mg/L, but lab values do not return any actual values that are below this level of detection. Unable to use the &quot;&lt;&quot; symbol.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="3.1">N/A indicates CRP levels are &lt; 3 mg/L, but lab values do not return any actual values that are below this level of detection. Unable to use the &quot;&lt;&quot; symbol.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from baseline to end of study, approximately 64 weeks.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Baricitinib Therapy</title>
          <description>4 milligrams oral Baricitinib daily for 52 weeks&#xD;
Baricitinib: 4 milligrams oral Baricitinib daily for 52 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="15"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
              </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="14" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema limbs - leg</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infection not requiring antibiotics</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Infection requiring antibiotics</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Matthew Koster, M.D.</name_or_title>
      <organization>Mayo Clinic</organization>
      <phone>507-284-5800</phone>
      <email>koster.matthew@mayo.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/NCT03026504
org study id: 16-008993
nct id: NCT03026504
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study will evaluate the safety and effectiveness of baricitinib in the treatment of
      giant cell arteritis. All participants will be taking prednisone at the start of the study.
      The prednisone will be reduced according to a standardized tapering schedule while
      participants continue to take one tablet of baricitinib daily for 52 weeks.
Baricitinib, an orally administered, potent, selective and reversible inhibitor of JAK1 and
      JAK2 has shown preliminary safety and efficacy in chronic, immune-mediated inflammatory
      conditions such as rheumatoid arthritis and psoriasis. This small molecule is uniquely suited
      as a potential novel therapeutic agent in GCA because of its suppressive effect on both the
      Th17 (IL-6, IL-23) andTh1 (IL-12, IFN-γ) pathways.

      This study will evaluate the safety and tolerability of baricitinib in a population of
      patients with relapsing GCA. The study is an open-label pilot study assessing the safety and
      tolerability of baricitinib (4 mg daily, oral, for 52 weeks) in addition to a standardized
      glucocorticoid taper. It is anticipated that adjunct baricitinib will be safe and well
      tolerated by patients with GCA and demonstrate preliminary efficacy as measured by reducing
      inflammatory markers, decreasing steroid requirements and increasing relapse-free survival.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse Events
time frame: 52 weeks
description: The percentage of subjects who experienced greater than or equal to one adverse event
measure: Giant Cell Arteritis (GCA) Relapse
time frame: 24 weeks, 52 weeks
description: The number of subjects to experience relapse of GCA at 24 weeks and 52 weeks. As defined as:
Presence of ESR ≥30 mm/hour and/or CRP ≥10 mg/L and the presence of at least one of the following:
Unequivocal cranial symptoms of GCA.
Unequivocal symptoms of PMR.
Other features judged by the clinician to be consistent with GCA or PMR (eg, fever of unknown origin, unexplained weight loss, fatigue/ malaise, etc) for which no other aetiology was identified as causational.
measure: Erythrocyte Sedimentation Rate (ESR)
time frame: week 0, week 24, week 52
description: ESR is a blood test that detects and monitors inflammation in the body. The normal range is 0 to 22 mm/hr for men and 0 to 29 mm/hr for women.
measure: C Reactive Protein (CRP)
time frame: week 0, week 24, week 52
description: C-reactive protein is a substance produced by the liver in response to inflammation. Normal blood CRP levels are below 3.0 mg/L.
arm group label: Baricitinib Therapy
arm group type: Experimental
description: 4 milligrams oral Baricitinib daily for 52 weeks
intervention type: Drug
intervention name: Baricitinib
description: 4 milligrams oral Baricitinib daily for 52 weeks
arm group label: Baricitinib Therapy
other name: JAK2 Inhibitor
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Kenneth Warrington, MD
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
responsible party type: Sponsor-Investigator
investigator affiliation: Mayo Clinic
investigator full name: Matthew J Koster
investigator title: MD
mesh term: Polymyalgia Rheumatica
mesh term: Giant Cell Arteritis
mesh term: Arteritis
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 