<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/NCT03800979</url>
  </required_header>
  <id_info>
    <org_study_id>IRB/IEB 004/2562</org_study_id>
    <nct_id>NCT03800979</nct_id>
  </id_info>
  <brief_title>Effectiveness and Safety of Tofacitinib in Patients With Extensive and Recalcitrant Alopecia Areata</brief_title>
  <official_title>Effectiveness and Safety of Tofacitinib in Patients With Extensive and Recalcitrant Alopecia Areata</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institute of Dermatology, Thailand</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institute of Dermatology, Thailand</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to assess the safety and efficacy of Tofacitinib in treating&#xD;
      patients with extensive and recalcitrant Alopecia Areata (AA), along with to evaluate the&#xD;
      economic impact of the patients that may be from changing in their quality of life. There are&#xD;
      patients with severe AA who may have little or no improvement from the treatment by&#xD;
      diphenylcyclopropenone (DPCP) or topical steroid with minoxidil but instead having positive&#xD;
      response from the treatment with Janus kinase(JAK) inhibitor such as Tofacitinib or&#xD;
      Ruxolitinib. For the best of my knowledge, there was no previous study in using Tofacitinib&#xD;
      to treat severe AA before in Thailand.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Alopecia areata (AA) or spot baldness, is a condition in which hair falls off from areas of&#xD;
      the body. It often happens on the scalp, causing a few bald spots and it may result in&#xD;
      psychological stress even though people are generally healthy. AA is believed to be an&#xD;
      autoimmune disease progressing from a breach in the immune privilege of the hair follicles&#xD;
      that causes hair to fall out in small patches, it may remain unnoticeable until the patches&#xD;
      eventually connect and then become noticeable. It can develop slowly, and also recur after&#xD;
      years between occurrences.&#xD;
&#xD;
      By standard AA treatment guideline, DPCP is the first treatment protocol and may follow with&#xD;
      anthralin or minoxidil. This oldy but goody treatment gives a good result of 75% in spotty&#xD;
      hair loss and 25% in total baldness. The new invention of treatment has been introduced in&#xD;
      the past 2 years by using JAK inhibitor, an oral medicine such as Tofacitinib and&#xD;
      Ruxolitinib. This treatment gives a good outcome so far in this short period of time,&#xD;
      54-81.9% of patients had over 50% increase of hair grows over the original protocol. The&#xD;
      theory is that JAK inhibitors would inhibit interferon-gamma and interleukin-15 signal&#xD;
      between white blood cell and hair follicle which reducing the rate of destroying hair&#xD;
      follicles.&#xD;
&#xD;
      The investigators propose the study to assess the safety and efficacy of Tofacitinib for&#xD;
      extensive and recalcitrant AA and to evaluate the economic impact effecting the AA patients.&#xD;
      Tofacitinib is an expensive medicine and needed to be taken up to 6 months to finish the&#xD;
      course to have a best outcome so it is not a popular choice of AA treatment at present time&#xD;
      unless it can show a promising result in recalcitrant AA.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 12, 2019</start_date>
  <completion_date type="Actual">January 30, 2021</completion_date>
  <primary_completion_date type="Actual">January 30, 2021</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>This is a Cohort study which all recruited volunteers will receive Tofacitinib for total of 24 weeks. The 19 volunteers are mixed male and female Thais who suffer from severe AA over 50% of the entire scalp.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Responders vs Non-Responders Using SALT Score</measure>
    <time_frame>48 weeks</time_frame>
    <description>The Severity of Alopecia Tool (SALT) is a measurement procedure used by dermatologists to determine the percentage of scalp hair loss. The SALT system divides the scalp into 4 areas: Top has 4 sections of 10% total are 40%, back has 4 sections of 6% total are 24% and the 2 sides, left and right, each has 2 sections of 4% and 2 sections of 5% total of 18% and 36% combined. In the beginning, the area of hair loss would be measured by checking each area for hair loss and determining the bald spots combined per SALT scale then keeping the record as SALT baseline (SALT). The total SALT score is measured 0-100%, with higher values representing greater hair loss.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Side Effects From Tofacitinib</measure>
    <time_frame>48 weeks</time_frame>
    <description>Patients came back for follow-up every month during a total of 24 weeks of treatments and at weeks 28,36 and 48.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Alopecia Areata</condition>
  <arm_group>
    <arm_group_label>Tofacitinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All participants will take Tofacitinib 5 mg twice daily for 24 weeks to treat extensive and recalcitrant alopecia areata.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tofacitinib</intervention_name>
    <description>Tofacitinib is an oral medicine in Janus kinase inhibitor 3 group which has been approved by FDA in treating Rheumatoid Arthritis. It has ability to inhibit nerve signal Interferon-ɣ and Interleukin-15 between white blood cell(WBC) and the nucleus of hair follicle cell causing the production of WBC type CD8+NKG2D+ T cell to slow down which this type of WBC is one of the cause of hair loss.</description>
    <arm_group_label>Tofacitinib</arm_group_label>
    <other_name>Xeljanz</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Thai volunteers age between 18 and 60 years old.&#xD;
&#xD;
          -  Volunteers must be patients who suffer from severe AA more than 50% of the entire&#xD;
             scalp.&#xD;
&#xD;
          -  Volunteers must be patients who are able to complete the monthly treatment at least in&#xD;
             the first 6 months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who suffer from other hair diseases such as: Telogen effluvium,&#xD;
             Trichotillomania, Tinea capitis&#xD;
&#xD;
          -  Patients who have other diseases that can have an impact on hair loss or temporary&#xD;
             hair loss condition with in 6 months prior to the study such as: thyroid problems,&#xD;
             liver disease, malnutrition, hearth disease, neurological disease, gastrointestinal&#xD;
             disorders, sexually transmitted disease, cancer, psychiatric disease.&#xD;
&#xD;
          -  Patients with AA who received treatment with either steroid, Anthralin or DPCP&#xD;
             application within 1 month before the selection or patients who had oral or injection&#xD;
             from steroid or other medication for hair loss treatment within 3 months before the&#xD;
             selection.&#xD;
&#xD;
          -  Woman with pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chinmanat Lekhavat, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institute of Dermatology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institute of Dermatology</name>
      <address>
        <city>Bangkok</city>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Thailand</country>
  </location_countries>
  <reference>
    <citation>Alkhalifah A, Alsantali A, Wang E, McElwee KJ, Shapiro J. Alopecia areata update: part II. Treatment. J Am Acad Dermatol. 2010 Feb;62(2):191-202, quiz 203-4. doi: 10.1016/j.jaad.2009.10.031.</citation>
    <PMID>20115946</PMID>
  </reference>
  <reference>
    <citation>Tosti A, Iorizzo M, Botta GL, Milani M. Efficacy and safety of a new clobetasol propionate 0.05% foam in alopecia areata: a randomized, double-blind placebo-controlled trial. J Eur Acad Dermatol Venereol. 2006 Nov;20(10):1243-7. doi: 10.1111/j.1468-3083.2006.01781.x.</citation>
    <PMID>17062039</PMID>
  </reference>
  <reference>
    <citation>Taylor CR, Hawk JL. PUVA treatment of alopecia areata partialis, totalis and universalis: audit of 10 years' experience at St John's Institute of Dermatology. Br J Dermatol. 1995 Dec;133(6):914-8. doi: 10.1111/j.1365-2133.1995.tb06925.x.</citation>
    <PMID>8547044</PMID>
  </reference>
  <reference>
    <citation>Liu LY, Craiglow BG, Dai F, King BA. Tofacitinib for the treatment of severe alopecia areata and variants: A study of 90 patients. J Am Acad Dermatol. 2017 Jan;76(1):22-28. doi: 10.1016/j.jaad.2016.09.007. Epub 2016 Nov 2.</citation>
    <PMID>27816293</PMID>
  </reference>
  <reference>
    <citation>Craiglow BG, Liu LY, King BA. Tofacitinib for the treatment of alopecia areata and variants in adolescents. J Am Acad Dermatol. 2017 Jan;76(1):29-32. doi: 10.1016/j.jaad.2016.09.006. Epub 2016 Nov 2.</citation>
    <PMID>27816292</PMID>
  </reference>
  <reference>
    <citation>Ibrahim O, Bayart CB, Hogan S, Piliang M, Bergfeld WF. Treatment of Alopecia Areata With Tofacitinib. JAMA Dermatol. 2017 Jun 1;153(6):600-602. doi: 10.1001/jamadermatol.2017.0001.</citation>
    <PMID>28355451</PMID>
  </reference>
  <reference>
    <citation>Divito SJ, Kupper TS. Inhibiting Janus kinases to treat alopecia areata. Nat Med. 2014 Sep;20(9):989-90. doi: 10.1038/nm.3685.</citation>
    <PMID>25198048</PMID>
  </reference>
  <results_reference>
    <citation>Alkhalifah A, Alsantali A, Wang E, McElwee KJ, Shapiro J. Alopecia areata update: part I. Clinical picture, histopathology, and pathogenesis. J Am Acad Dermatol. 2010 Feb;62(2):177-88, quiz 189-90. doi: 10.1016/j.jaad.2009.10.032.</citation>
    <PMID>20115945</PMID>
  </results_reference>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 10, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 11, 2019</study_first_posted>
  <results_first_submitted>January 23, 2022</results_first_submitted>
  <results_first_submitted_qc>February 15, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">March 10, 2022</results_first_posted>
  <last_update_submitted>March 28, 2022</last_update_submitted>
  <last_update_submitted_qc>March 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 31, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Institute of Dermatology, Thailand</investigator_affiliation>
    <investigator_full_name>Chinmanat Lekhavat</investigator_full_name>
    <investigator_title>Assistant Director of Institute of Dermatology</investigator_title>
  </responsible_party>
  <keyword>Alopecia areata</keyword>
  <keyword>Alopecia universalis</keyword>
  <keyword>Alopecia totalis</keyword>
  <keyword>Tofacitinib</keyword>
  <keyword>JAK inhibitor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alopecia</mesh_term>
    <mesh_term>Alopecia Areata</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tofacitinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>August 27, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/79/NCT03800979/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Nineteen participants who met the inclusion criteria were enrolled and received 10 mg/day oral tofacitinib.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Tofacitinib</title>
          <description>All participants will take Tofacitinib 5 mg twice daily for 24 weeks to treat extensive and recalcitrant alopecia areata.&#xD;
Tofacitinib: Tofacitinib is an oral medicine in the Janus kinase inhibitor 3 groups which FDA has approved in treating Rheumatoid Arthritis. It can inhibit nerve signal Interferon-ɣ and Interleukin-15 between white blood cell(WBC) and the nucleus of hair follicle cell causing the production of WBC type CD8+NKG2D+ T cell to slow down which this type of WBC is one of the causes of hair loss.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Tofacitinib</title>
          <description>All participants will take Tofacitinib 5 mg twice daily for 24 weeks to treat extensive and recalcitrant alopecia areata.&#xD;
Tofacitinib is the Janus kinase inhibitor, which FDA has approved for Rheumatoid Arthritis. It can inhibit nerve signal Interferon-ɣ and Interleukin-15 between white blood cell(WBC) and the nucleus of hair follicle cell causing the production of WBC type CD8+NKG2D+ T cell to slow down which this type of WBC is one of the causes of hair loss.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="19"/>
          </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="32.68" spread="8.75"/>
                  </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="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Thailand</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline SALT score</title>
          <description>Baseline SALT (Severity of Alopecia Tool) score is the percentage of hair loss. The total SALT score is measured 0-100%, with higher values representing greater hair loss.</description>
          <units>score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="95.11" spread="14.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Responders vs Non-Responders Using SALT Score</title>
        <description>The Severity of Alopecia Tool (SALT) is a measurement procedure used by dermatologists to determine the percentage of scalp hair loss. The SALT system divides the scalp into 4 areas: Top has 4 sections of 10% total are 40%, back has 4 sections of 6% total are 24% and the 2 sides, left and right, each has 2 sections of 4% and 2 sections of 5% total of 18% and 36% combined. In the beginning, the area of hair loss would be measured by checking each area for hair loss and determining the bald spots combined per SALT scale then keeping the record as SALT baseline (SALT). The total SALT score is measured 0-100%, with higher values representing greater hair loss.</description>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tofacitinib</title>
            <description>All participants will take Tofacitinib 5 mg twice daily for 24 weeks to treat extensive and recalcitrant alopecia areata.&#xD;
Tofacitinib: Tofacitinib is an oral medicine in the Janus kinase inhibitor 3 groups which FDA has approved in treating Rheumatoid Arthritis. It can inhibit nerve signal Interferon-ɣ and Interleukin-15 between white blood cell(WBC) and the nucleus of hair follicle cell causing the production of WBC type CD8+NKG2D+ T cell to slow down which this type of WBC is one of the causes of hair loss.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Responders vs Non-Responders Using SALT Score</title>
          <description>The Severity of Alopecia Tool (SALT) is a measurement procedure used by dermatologists to determine the percentage of scalp hair loss. The SALT system divides the scalp into 4 areas: Top has 4 sections of 10% total are 40%, back has 4 sections of 6% total are 24% and the 2 sides, left and right, each has 2 sections of 4% and 2 sections of 5% total of 18% and 36% combined. In the beginning, the area of hair loss would be measured by checking each area for hair loss and determining the bald spots combined per SALT scale then keeping the record as SALT baseline (SALT). The total SALT score is measured 0-100%, with higher values representing greater hair loss.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Responders (SALT score improved &gt;=50%)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Non-responders (SALT score improved &lt; 50%)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Side Effects From Tofacitinib</title>
        <description>Patients came back for follow-up every month during a total of 24 weeks of treatments and at weeks 28,36 and 48.</description>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tofacitinib</title>
            <description>All participants will take Tofacitinib 5 mg twice daily for 24 weeks to treat extensive and recalcitrant alopecia areata.&#xD;
Tofacitinib: Tofacitinib is an oral medicine in the Janus kinase inhibitor 3 groups which FDA has approved in treating Rheumatoid Arthritis. It can inhibit nerve signal Interferon-ɣ and Interleukin-15 between white blood cell(WBC) and the nucleus of hair follicle cell causing the production of WBC type CD8+NKG2D+ T cell to slow down which this type of WBC is one of the causes of hair loss.</description>
          </group>
        </group_list>
        <measure>
          <title>Side Effects From Tofacitinib</title>
          <description>Patients came back for follow-up every month during a total of 24 weeks of treatments and at weeks 28,36 and 48.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Dyslipidemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Upper respiratory tract infection</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tuberculosis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Myalgia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Acne</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Weight gain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Constipation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Patients came back for follow-up every month during a total of 24 weeks of treatments and at weeks 28,36 and 48.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Tofacitinib</title>
          <description>All participants will take Tofacitinib 5 mg twice daily for 24 weeks to treat extensive and recalcitrant alopecia areata.&#xD;
Tofacitinib: Tofacitinib is an oral medicine in the Janus kinase inhibitor 3 groups which FDA has approved in treating Rheumatoid Arthritis. It can inhibit nerve signal Interferon-ɣ and Interleukin-15 between white blood cell(WBC) and the nucleus of hair follicle cell causing the production of WBC type CD8+NKG2D+ T cell to slow down which this type of WBC is one of the causes of hair loss.</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="19"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Intestinal tuberculosis</sub_title>
                <description>Ileal tuberculosis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</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="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <description>Upper respiratory tract infection such as common cold</description>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dyslipidemia</sub_title>
                <description>Dyslipidemia (mild)</description>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Weight gain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <description>Myalgia</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Chinmanat Lekhavat (My old last name is Tangjaturonrusamee.)</name_or_title>
      <organization>Institute of Dermatology</organization>
      <phone>+660847607474</phone>
      <email>chinmanat@hotmail.com</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/NCT03800979
org study id: IRB/IEB 004/2562
nct id: NCT03800979
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The objective of this study is to assess the safety and efficacy of Tofacitinib in treating
      patients with extensive and recalcitrant Alopecia Areata (AA), along with to evaluate the
      economic impact of the patients that may be from changing in their quality of life. There are
      patients with severe AA who may have little or no improvement from the treatment by
      diphenylcyclopropenone (DPCP) or topical steroid with minoxidil but instead having positive
      response from the treatment with Janus kinase(JAK) inhibitor such as Tofacitinib or
      Ruxolitinib. For the best of my knowledge, there was no previous study in using Tofacitinib
      to treat severe AA before in Thailand.
Alopecia areata (AA) or spot baldness, is a condition in which hair falls off from areas of
      the body. It often happens on the scalp, causing a few bald spots and it may result in
      psychological stress even though people are generally healthy. AA is believed to be an
      autoimmune disease progressing from a breach in the immune privilege of the hair follicles
      that causes hair to fall out in small patches, it may remain unnoticeable until the patches
      eventually connect and then become noticeable. It can develop slowly, and also recur after
      years between occurrences.

      By standard AA treatment guideline, DPCP is the first treatment protocol and may follow with
      anthralin or minoxidil. This oldy but goody treatment gives a good result of 75% in spotty
      hair loss and 25% in total baldness. The new invention of treatment has been introduced in
      the past 2 years by using JAK inhibitor, an oral medicine such as Tofacitinib and
      Ruxolitinib. This treatment gives a good outcome so far in this short period of time,
      54-81.9% of patients had over 50% increase of hair grows over the original protocol. The
      theory is that JAK inhibitors would inhibit interferon-gamma and interleukin-15 signal
      between white blood cell and hair follicle which reducing the rate of destroying hair
      follicles.

      The investigators propose the study to assess the safety and efficacy of Tofacitinib for
      extensive and recalcitrant AA and to evaluate the economic impact effecting the AA patients.
      Tofacitinib is an expensive medicine and needed to be taken up to 6 months to finish the
      course to have a best outcome so it is not a popular choice of AA treatment at present time
      unless it can show a promising result in recalcitrant AA.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This is a Cohort study which all recruited volunteers will receive Tofacitinib for total of 24 weeks. The 19 volunteers are mixed male and female Thais who suffer from severe AA over 50% of the entire scalp.
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Responders vs Non-Responders Using SALT Score
time frame: 48 weeks
description: The Severity of Alopecia Tool (SALT) is a measurement procedure used by dermatologists to determine the percentage of scalp hair loss. The SALT system divides the scalp into 4 areas: Top has 4 sections of 10% total are 40%, back has 4 sections of 6% total are 24% and the 2 sides, left and right, each has 2 sections of 4% and 2 sections of 5% total of 18% and 36% combined. In the beginning, the area of hair loss would be measured by checking each area for hair loss and determining the bald spots combined per SALT scale then keeping the record as SALT baseline (SALT). The total SALT score is measured 0-100%, with higher values representing greater hair loss.
measure: Side Effects From Tofacitinib
time frame: 48 weeks
description: Patients came back for follow-up every month during a total of 24 weeks of treatments and at weeks 28,36 and 48.
arm group label: Tofacitinib
arm group type: Experimental
description: All participants will take Tofacitinib 5 mg twice daily for 24 weeks to treat extensive and recalcitrant alopecia areata.
intervention type: Drug
intervention name: Tofacitinib
description: Tofacitinib is an oral medicine in Janus kinase inhibitor 3 group which has been approved by FDA in treating Rheumatoid Arthritis. It has ability to inhibit nerve signal Interferon-ɣ and Interleukin-15 between white blood cell(WBC) and the nucleus of hair follicle cell causing the production of WBC type CD8+NKG2D+ T cell to slow down which this type of WBC is one of the cause of hair loss.
arm group label: Tofacitinib
other name: Xeljanz
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Chinmanat Lekhavat, MD
role: Principal Investigator
affiliation: Institute of Dermatology
facility: 
country: Thailand
citation: Alkhalifah A, Alsantali A, Wang E, McElwee KJ, Shapiro J. Alopecia areata update: part II. Treatment. J Am Acad Dermatol. 2010 Feb;62(2):191-202, quiz 203-4. doi: 10.1016/j.jaad.2009.10.031.
PMID: 20115946
citation: Tosti A, Iorizzo M, Botta GL, Milani M. Efficacy and safety of a new clobetasol propionate 0.05% foam in alopecia areata: a randomized, double-blind placebo-controlled trial. J Eur Acad Dermatol Venereol. 2006 Nov;20(10):1243-7. doi: 10.1111/j.1468-3083.2006.01781.x.
PMID: 17062039
citation: Taylor CR, Hawk JL. PUVA treatment of alopecia areata partialis, totalis and universalis: audit of 10 years' experience at St John's Institute of Dermatology. Br J Dermatol. 1995 Dec;133(6):914-8. doi: 10.1111/j.1365-2133.1995.tb06925.x.
PMID: 8547044
citation: Liu LY, Craiglow BG, Dai F, King BA. Tofacitinib for the treatment of severe alopecia areata and variants: A study of 90 patients. J Am Acad Dermatol. 2017 Jan;76(1):22-28. doi: 10.1016/j.jaad.2016.09.007. Epub 2016 Nov 2.
PMID: 27816293
citation: Craiglow BG, Liu LY, King BA. Tofacitinib for the treatment of alopecia areata and variants in adolescents. J Am Acad Dermatol. 2017 Jan;76(1):29-32. doi: 10.1016/j.jaad.2016.09.006. Epub 2016 Nov 2.
PMID: 27816292
citation: Ibrahim O, Bayart CB, Hogan S, Piliang M, Bergfeld WF. Treatment of Alopecia Areata With Tofacitinib. JAMA Dermatol. 2017 Jun 1;153(6):600-602. doi: 10.1001/jamadermatol.2017.0001.
PMID: 28355451
citation: Divito SJ, Kupper TS. Inhibiting Janus kinases to treat alopecia areata. Nat Med. 2014 Sep;20(9):989-90. doi: 10.1038/nm.3685.
PMID: 25198048
citation: Alkhalifah A, Alsantali A, Wang E, McElwee KJ, Shapiro J. Alopecia areata update: part I. Clinical picture, histopathology, and pathogenesis. J Am Acad Dermatol. 2010 Feb;62(2):177-88, quiz 189-90. doi: 10.1016/j.jaad.2009.10.032.
PMID: 20115945
responsible party type: Principal Investigator
investigator affiliation: Institute of Dermatology, Thailand
investigator full name: Chinmanat Lekhavat
investigator title: Assistant Director of Institute of Dermatology
mesh term: Alopecia
mesh term: Alopecia Areata
mesh term: Tofacitinib
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 