<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/NCT04431895</url>
  </required_header>
  <id_info>
    <org_study_id>KY2020-019</org_study_id>
    <nct_id>NCT04431895</nct_id>
  </id_info>
  <brief_title>Safety And Efficacy Of Tofacitinib In Patients With Refractory Myasthenia Gravis: A Pilot Study</brief_title>
  <official_title>A Prospective,Single-center,Single-Arm,Single-Blind Pilot Study To Investigate The Efficacy Of Tofacitinib In Patients With Refractory Myasthenia Gravis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Huashan Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Huashan Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a 6 month study that will evaluate the efficacy of 5mg tofacitinib tablet taken twice&#xD;
      a day in patients with refractory myasthenia gravis. Twenty adult participants will receive a&#xD;
      four month treatment of tofacitinib followed by elution for one month.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 11, 2020</start_date>
  <completion_date type="Anticipated">February 9, 2023</completion_date>
  <primary_completion_date type="Anticipated">February 4, 2023</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Quantitative Myasthenia Gravis (QMG) Scores at Month 6</measure>
    <time_frame>Baseline, Month 6</time_frame>
    <description>A quantitative MG scoring system (QMG Score) is essential in the objective evaluation of therapy for MG.This scoring system is based on quantitative testing of sentinel muscle groups. Total QMG score range from 0 (extreme disease severity) to 39 (none), higher score indicated less disease severity.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Myasthenia Gravis-related Activities of Daily Living (MG-ADL) Scores at Month 6</measure>
    <time_frame>Baseline, Month 6</time_frame>
    <description>The myasthenia gravis activities of daily living (MG-ADL) profile is an eight-item patient-reported scale developed to assess MG symptoms and their effects on daily activities.Total MG-ADL score range from 0 (none) to 24 (extreme disease conditions), higher score indicated more disease severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Manual Muscle Testing (MMT) Scores at Month 6</measure>
    <time_frame>Baseline, Month 6</time_frame>
    <description>The MMT score is the sum of strength or function values assigned by the examining physician to 30 muscle groups usually affected by MG. Total MMT score range from 0 (none) to 124 (extreme muscle weakness), higher score indicated more disease severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Myasthenia Gravis-Quality of Life Questionnaire-15 item (MG-QOL15) Scores at Month 6</measure>
    <time_frame>Baseline, Month 6</time_frame>
    <description>The MG-QOL15 is helpful in informing the clinician about the patient's perception of the extent of and dissatisfaction with MG-related dysfunction. Total MG-QOL15 score range from 0 (none) to 60 (extreme disease severity), higher score indicated more disease severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Doses of Steroids at Month 6</measure>
    <time_frame>Baseline, Month 6</time_frame>
    <description>Steroids is recommended as the first-line treatment for myasthenia gravis. Here we followed the combined doseage of steroids while administrating tofacitinib for enrolled participants.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change From Baseline in Serum Titers of anti-acetylcholine receptor antibodies at Month 6</measure>
    <time_frame>Baseline, Month 6</time_frame>
    <description>Anti-acetylcholine receptor antibodies are the major pathological autoantibodies of MG. For anti-AChR antibodies-positive candidates, we followed the antibodies titers at Month 6.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change From Baseline in Inflammatory Cytokines at Month 6</measure>
    <time_frame>Baseline, Month 6</time_frame>
    <description>MG is an autoimmune disease manifested by impairment at the neuromuscular junction featured by weakness and fatigability. We compared the inflammatory cytokines (IL-1β,IL-2,IL-4,IL-5,IL-6,IL-9,IL-10,IL-12p70,IL-13,IL-17A,IL-18,IL-21,IL-22,IL-23,IL-27,IFN-gamma,TNF-α and GM-CSF) at Baseline and Month 6.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Myasthenia Gravis, Generalized</condition>
  <arm_group>
    <arm_group_label>tofacitinib 5mg twice a day</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tofacitinib 5 MG</intervention_name>
    <description>tofacitinib 5 mg tablet administered twice a day for 6 months</description>
    <arm_group_label>tofacitinib 5mg twice a day</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  fluctuating muscle weakness and fatigability classified as the Myasthenia Gravis&#xD;
             Foundation of America (MGFA) clinical classification Type IIa-IVa;&#xD;
&#xD;
          -  more than 10% amplitude decrement in low frequency repetitive nerve stimulation, and&#xD;
             less than 10% amplitude increment in high frequency repetitive nerve stimulation;&#xD;
&#xD;
          -  understanding and assigning the informed consent form, and having a good compliance&#xD;
             with treatment.&#xD;
&#xD;
        meet all of the criteria in above as well as at least one of the below:&#xD;
&#xD;
          -  refractory: insufficient response to full dose- and course- steroids treatment&#xD;
             (0.75-1mg per kg per day for at least 3-6 months), failure to respond adequately to&#xD;
             tacrolimus (no less than 3mg per day) for 3 months;&#xD;
&#xD;
          -  severe or intolerable adverse effects from conventional immunosuppressive therapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  positive for muscle-specific kinase (MuSK) antibodies;&#xD;
&#xD;
          -  a tumor history except for thymoma;&#xD;
&#xD;
          -  a history of Type B and Type C hepatitis;&#xD;
&#xD;
          -  a history of tuberculosis or T-SPOT.TB tset positivity;&#xD;
&#xD;
          -  hepatic, renal and cardial insufficiency (baseline: ALT/AST&gt;50U/L;BNP&gt;200pg/ml）;&#xD;
&#xD;
          -  severe allergy or infection, or chronic or recurrent infection;&#xD;
&#xD;
          -  pregnancy;&#xD;
&#xD;
          -  hyperlipidemia;&#xD;
&#xD;
          -  participating other clinical trials&#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_contact>
    <last_name>Chongbo Zhao, MD</last_name>
    <phone>86-21-52889999</phone>
    <email>zhao_chongbo@fudan.edu.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Chong Yan, MD</last_name>
    <phone>86-21-52889999</phone>
    <email>yanc_huashan@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Huashan Hospital</name>
      <address>
        <city>Shanghai</city>
        <zip>200040</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chongbo Zhao, MD</last_name>
      <phone>+86 21 52889999</phone>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>June 12, 2020</study_first_submitted>
  <study_first_submitted_qc>June 12, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>September 1, 2022</last_update_submitted>
  <last_update_submitted_qc>September 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Huashan Hospital</investigator_affiliation>
    <investigator_full_name>Chongbo Zhao</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>myasthenia gravis</keyword>
  <keyword>tofacitinib</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Myasthenia Gravis</mesh_term>
    <mesh_term>Muscle Weakness</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>
    <ipd_description>Individual participant data (IPD) are not available to other researchers.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04431895
org study id: KY2020-019
nct id: NCT04431895
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a 6 month study that will evaluate the efficacy of 5mg tofacitinib tablet taken twice
      a day in patients with refractory myasthenia gravis. Twenty adult participants will receive a
      four month treatment of tofacitinib followed by elution for one month.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change From Baseline in Quantitative Myasthenia Gravis (QMG) Scores at Month 6
time frame: Baseline, Month 6
description: A quantitative MG scoring system (QMG Score) is essential in the objective evaluation of therapy for MG.This scoring system is based on quantitative testing of sentinel muscle groups. Total QMG score range from 0 (extreme disease severity) to 39 (none), higher score indicated less disease severity.
measure: Change From Baseline in Myasthenia Gravis-related Activities of Daily Living (MG-ADL) Scores at Month 6
time frame: Baseline, Month 6
description: The myasthenia gravis activities of daily living (MG-ADL) profile is an eight-item patient-reported scale developed to assess MG symptoms and their effects on daily activities.Total MG-ADL score range from 0 (none) to 24 (extreme disease conditions), higher score indicated more disease severity.
measure: Change From Baseline in Manual Muscle Testing (MMT) Scores at Month 6
time frame: Baseline, Month 6
description: The MMT score is the sum of strength or function values assigned by the examining physician to 30 muscle groups usually affected by MG. Total MMT score range from 0 (none) to 124 (extreme muscle weakness), higher score indicated more disease severity.
measure: Change From Baseline in Myasthenia Gravis-Quality of Life Questionnaire-15 item (MG-QOL15) Scores at Month 6
time frame: Baseline, Month 6
description: The MG-QOL15 is helpful in informing the clinician about the patient's perception of the extent of and dissatisfaction with MG-related dysfunction. Total MG-QOL15 score range from 0 (none) to 60 (extreme disease severity), higher score indicated more disease severity.
measure: Change From Baseline in Doses of Steroids at Month 6
time frame: Baseline, Month 6
description: Steroids is recommended as the first-line treatment for myasthenia gravis. Here we followed the combined doseage of steroids while administrating tofacitinib for enrolled participants.
measure: Change From Baseline in Serum Titers of anti-acetylcholine receptor antibodies at Month 6
time frame: Baseline, Month 6
description: Anti-acetylcholine receptor antibodies are the major pathological autoantibodies of MG. For anti-AChR antibodies-positive candidates, we followed the antibodies titers at Month 6.
measure: Change From Baseline in Inflammatory Cytokines at Month 6
time frame: Baseline, Month 6
description: MG is an autoimmune disease manifested by impairment at the neuromuscular junction featured by weakness and fatigability. We compared the inflammatory cytokines (IL-1β,IL-2,IL-4,IL-5,IL-6,IL-9,IL-10,IL-12p70,IL-13,IL-17A,IL-18,IL-21,IL-22,IL-23,IL-27,IFN-gamma,TNF-α and GM-CSF) at Baseline and Month 6.
arm group label: tofacitinib 5mg twice a day
arm group type: Experimental
intervention type: Drug
intervention name: Tofacitinib 5 MG
description: tofacitinib 5 mg tablet administered twice a day for 6 months
arm group label: tofacitinib 5mg twice a day
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Chongbo Zhao, MD
phone: 86-21-52889999
email: zhao_chongbo@fudan.edu.cn
last name: Chong Yan, MD
phone: 86-21-52889999
email: yanc_huashan@163.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Huashan Hospital
investigator full name: Chongbo Zhao
investigator title: Professor
mesh term: Myasthenia Gravis
mesh term: Muscle Weakness
mesh term: Tofacitinib
sharing ipd: No
ipd description: Individual participant data (IPD) are not available to other researchers.