xml: <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/NCT06011343</url>
    </required_header>
    <id_info>
      <org_study_id>CL Tofa23</org_study_id>
      <nct_id>NCT06011343</nct_id>
    </id_info>
    <brief_title>Tofacitinib Associated With Meglumine Antimoniate in Cutaneous Leishmaniasis</brief_title>
    <acronym>CLTofa23</acronym>
    <official_title>Tofacitinib Associated With Meglumine Antimoniate in the Control of American Tegumentary Leishmaniasis. A Randomized and Controlled Clinical Trial.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Hospital Universitário Professor Edgard Santos</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Instituto Gonçalo Muniz FIOCRUZ BA</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Hospital Universitário Professor Edgard Santos</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>
        Phase 2/3 randomized and controlled clinical trial, which will evaluate the effectiveness of&#xD;
        the association meglumine antimoniate (Glucantime) with tofacitinib in the cure of CL and the&#xD;
        capacity of this association to reduce the time of cure of the disease.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        1. STUDY AREA The southeastern region of the State of Bahia, Brazil, where the village of&#xD;
             Corte de Pedra and adjacent towns are located, is one of the most important American&#xD;
             Tegumentary Leishmaniasis (ATL) endemic area in Latin America. The Corte de Pedra Health&#xD;
             Center, in the municipality of Tancredo Neves, is located 280km from Salvador and is a&#xD;
             Reference Center for Diagnosis and Treatment of ATL. Yearly, more than 500 cases of&#xD;
             patients with ATL are diagnosed and treated at this Center.&#xD;
  &#xD;
             The Health Center was established in 1986 and clinical physicians, dermatologists,&#xD;
             otorhinolaryngologists and immunologists from the Immunology Service of the Federal&#xD;
             University of Bahia, the Gonçalo Moniz Institute (IGM) and the Federal University of&#xD;
             Recôncavo Bahiano (UFRB) visit the area every two weeks. The Post also has the support&#xD;
             of 4 trained health agents, all residents of the region. They assist patients, visit&#xD;
             families, and participate in research activities.&#xD;
  &#xD;
          2. STUDY DESIGN&#xD;
  &#xD;
             A. Type of study:&#xD;
  &#xD;
             This project is a phase 2/3 randomized and controlled clinical trial, which will&#xD;
             evaluate the effectiveness of the association meglumine antimoniate (Glucantime) with&#xD;
             tofacitinib in the cure of CL. the main objectives are: 1. To compare the cure rate of&#xD;
             meglumine antimoniate associated with tofacitinib with meglumine antimoniate alone in&#xD;
             the treatment of CL caused by L. braziliensis; 2. To determine whether combined&#xD;
             treatment with meglumine antimoniate associated with tofacitinib reduces CL healing&#xD;
             time.&#xD;
  &#xD;
             B. Definition of cases:&#xD;
  &#xD;
             Cutaneous Leishmaniasis: Presence of a typical ulcerated lesion on the skin, without&#xD;
             evidence of mucosal involvement, with a positive skin test and disease duration between&#xD;
             30 and 90 days. The diagnosis will be made by identifying amastigotes in the&#xD;
             histopathological study with immunohistochemistry and/or documentation of DNA for&#xD;
             L.braziliensis by polymerase chain reaction (PCR).&#xD;
  &#xD;
             C. Methodology:&#xD;
  &#xD;
             The rate of cure or treatment failure is only defined on day 90 after starting therapy.&#xD;
             We estimate that combining Glucantime with tofacitinib will increase the healing rate&#xD;
             and reduce the healing time of CL. The present proposal is a proof of concept with the&#xD;
             participation of patients with CL with disease duration between 30 and 90 days and with&#xD;
             ulcer size between 10 and 60mm. Patients will be randomized, group 1 will receive&#xD;
             Glucantime at a dose of 20mg/Kg/weight /day with a maximum dose of 1200mg intravenously&#xD;
             for 20 days, and group 2 will be treated with Glucantime at the dose and time period&#xD;
             described above associated with tofacitinib at a dose of 10mg/day for 30 days. Patients&#xD;
             will be evaluated on day 0, day 30, day 60 and day 90 to determine the size and&#xD;
             characteristics of the ulcers and the occurrence of wound healing.&#xD;
  &#xD;
             Sample size calculation: Considering that healing of ulcers up to 60mm in diameter in&#xD;
             patients with CL with Glucantime will occur in 50% of patients while the cure rate in&#xD;
             patients receiving Glucantime combined with tofacitinib will be 90% with a power of 80%&#xD;
             and P&lt; 0.05, 22 patients will be needed, 11 in each group.&#xD;
  &#xD;
             Subjects will be allocated in the 2 study arms after randomization at&#xD;
             www.randomization.com.&#xD;
  &#xD;
          3. ETHICAL CONSIDERATIONS Participation in the study is voluntary and all participants&#xD;
             must, after reading and understanding the nature of the study, benefits and risks, sign&#xD;
             the attached Free and Informed Consent Form (TCLE). This study was approved by the&#xD;
             ethics committee of the Faculty of Medicine of Bahia, Federal University of Bahia.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">July 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">October 1, 2024</primary_completion_date>
    <phase>Phase 2/Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>CL patients will be allocated in 2 intervention groups.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
      <masking_description>After randomization and allocation each patient will receive a code that will be confidential.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Cure at 90 days</measure>
      <time_frame>90 days</time_frame>
      <description>Healing will be defined by complete healing of the ulcer and re-epithelialization of the skin on day 90, in the absence of infiltrated borders. Failure will be defined as persistence of the ulcer at day 90 with ulcer healing occurring but persistent infiltration at the edges.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Cure at 180 days</measure>
      <time_frame>180 days</time_frame>
      <description>Absence of relapse after 180 days</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to cure</measure>
      <time_frame>Days</time_frame>
      <description>Time (in days) until complete healing of the ulcer and re-epithelialization of the skin in the absence of infiltrated borders.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adverse events</measure>
      <time_frame>45 dyas</time_frame>
      <description>Adverse events will be recorded and graded</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">22</enrollment>
    <condition>Cutaneous Leishmaniasis, American</condition>
    <arm_group>
      <arm_group_label>Placebo and Sbv</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Eleven CL patients will receive meglumine antimoniate by EV route at 20mg/kg/day, for 20 days.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Tofacitinib and Sbv</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Eleven CL patients will receive oral tofatinib (10mg daily for 30 days) associated to meglumine antimoniate by EV route at 20mg/kg/day, for 20 days.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Oral tofacitinib</intervention_name>
      <description>Association of tofacitinib and meglumine antimoniate</description>
      <arm_group_label>Tofacitinib and Sbv</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Parenteral meglumine antimoniate</intervention_name>
      <description>Meglumine antimoniate</description>
      <arm_group_label>Placebo and Sbv</arm_group_label>
      <arm_group_label>Tofacitinib and Sbv</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Subjects with CL of both sexes with disease duration between 30 and 90 days. Patients&#xD;
               with CL will be treatment-naïve for leishmaniasis. Individuals will be explained about&#xD;
               the nature of the study and will only be included if they agree to participate and&#xD;
               sign the Free and Informed Consent Form.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients under the age of 18 and pregnant women will not participate in the study&#xD;
               considering the need to withdraw 30 ml of blood to carry out the studies of the immune&#xD;
               response. Patients over 60 years old, debilitating chronic diseases such as heart&#xD;
               failure, liver failure, kidney failure, HIV infection and use of immunosuppressant&#xD;
               drugs will also not participate in the study.&#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>EDGAR CARVALHO, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Federal University of Bahia</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>EDGAR L CARVALHO, MD, PhD</last_name>
      <phone>7132377353</phone>
      <email>imuno@ufba.br</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>PAULO R LIMA MACHADO, MD, PhD</last_name>
      <phone>7132377353</phone>
      <email>19pmachado@gmail.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Corte de Pedra Health Post</name>
        <address>
          <city>Presidente Tancredo Neves</city>
          <state>Bahia</state>
          <zip>40000</zip>
          <country>Brazil</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Brazil</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 21, 2023</study_first_submitted>
    <study_first_submitted_qc>August 21, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 25, 2023</study_first_posted>
    <last_update_submitted>August 21, 2023</last_update_submitted>
    <last_update_submitted_qc>August 21, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 25, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Hospital Universitário Professor Edgard Santos</investigator_affiliation>
      <investigator_full_name>Paulo Roberto Lima Machado</investigator_full_name>
      <investigator_title>Senior Researcher</investigator_title>
    </responsible_party>
    <keyword>Cutaneous Leishmaniasis, meglumine antimoniate, tofacitinib</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Leishmaniasis</mesh_term>
      <mesh_term>Leishmaniasis, Cutaneous</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Meglumine Antimoniate</mesh_term>
      <mesh_term>Tofacitinib</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>There is not a plan to make IPD available.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06011343
  org study id: CL Tofa23
  nct id: NCT06011343
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Phase 2/3 randomized and controlled clinical trial, which will evaluate the effectiveness of
        the association meglumine antimoniate (Glucantime) with tofacitinib in the cure of CL and the
        capacity of this association to reduce the time of cure of the disease.
  1. STUDY AREA The southeastern region of the State of Bahia, Brazil, where the village of
             Corte de Pedra and adjacent towns are located, is one of the most important American
             Tegumentary Leishmaniasis (ATL) endemic area in Latin America. The Corte de Pedra Health
             Center, in the municipality of Tancredo Neves, is located 280km from Salvador and is a
             Reference Center for Diagnosis and Treatment of ATL. Yearly, more than 500 cases of
             patients with ATL are diagnosed and treated at this Center.
  
             The Health Center was established in 1986 and clinical physicians, dermatologists,
             otorhinolaryngologists and immunologists from the Immunology Service of the Federal
             University of Bahia, the Gonçalo Moniz Institute (IGM) and the Federal University of
             Recôncavo Bahiano (UFRB) visit the area every two weeks. The Post also has the support
             of 4 trained health agents, all residents of the region. They assist patients, visit
             families, and participate in research activities.
  
          2. STUDY DESIGN
  
             A. Type of study:
  
             This project is a phase 2/3 randomized and controlled clinical trial, which will
             evaluate the effectiveness of the association meglumine antimoniate (Glucantime) with
             tofacitinib in the cure of CL. the main objectives are: 1. To compare the cure rate of
             meglumine antimoniate associated with tofacitinib with meglumine antimoniate alone in
             the treatment of CL caused by L. braziliensis; 2. To determine whether combined
             treatment with meglumine antimoniate associated with tofacitinib reduces CL healing
             time.
  
             B. Definition of cases:
  
             Cutaneous Leishmaniasis: Presence of a typical ulcerated lesion on the skin, without
             evidence of mucosal involvement, with a positive skin test and disease duration between
             30 and 90 days. The diagnosis will be made by identifying amastigotes in the
             histopathological study with immunohistochemistry and/or documentation of DNA for
             L.braziliensis by polymerase chain reaction (PCR).
  
             C. Methodology:
  
             The rate of cure or treatment failure is only defined on day 90 after starting therapy.
             We estimate that combining Glucantime with tofacitinib will increase the healing rate
             and reduce the healing time of CL. The present proposal is a proof of concept with the
             participation of patients with CL with disease duration between 30 and 90 days and with
             ulcer size between 10 and 60mm. Patients will be randomized, group 1 will receive
             Glucantime at a dose of 20mg/Kg/weight /day with a maximum dose of 1200mg intravenously
             for 20 days, and group 2 will be treated with Glucantime at the dose and time period
             described above associated with tofacitinib at a dose of 10mg/day for 30 days. Patients
             will be evaluated on day 0, day 30, day 60 and day 90 to determine the size and
             characteristics of the ulcers and the occurrence of wound healing.
  
             Sample size calculation: Considering that healing of ulcers up to 60mm in diameter in
             patients with CL with Glucantime will occur in 50% of patients while the cure rate in
             patients receiving Glucantime combined with tofacitinib will be 90% with a power of 80%
             and P< 0.05, 22 patients will be needed, 11 in each group.
  
             Subjects will be allocated in the 2 study arms after randomization at
             www.randomization.com.
  
          3. ETHICAL CONSIDERATIONS Participation in the study is voluntary and all participants
             must, after reading and understanding the nature of the study, benefits and risks, sign
             the attached Free and Informed Consent Form (TCLE). This study was approved by the
             ethics committee of the Faculty of Medicine of Bahia, Federal University of Bahia.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: CL patients will be allocated in 2 intervention groups.
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  masking description: After randomization and allocation each patient will receive a code that will be confidential.
  measure: Cure at 90 days
  time frame: 90 days
  description: Healing will be defined by complete healing of the ulcer and re-epithelialization of the skin on day 90, in the absence of infiltrated borders. Failure will be defined as persistence of the ulcer at day 90 with ulcer healing occurring but persistent infiltration at the edges.
  measure: Cure at 180 days
  time frame: 180 days
  description: Absence of relapse after 180 days
  measure: Time to cure
  time frame: Days
  description: Time (in days) until complete healing of the ulcer and re-epithelialization of the skin in the absence of infiltrated borders.
  measure: Adverse events
  time frame: 45 dyas
  description: Adverse events will be recorded and graded
  arm group label: Placebo and Sbv
  arm group type: Placebo Comparator
  description: Eleven CL patients will receive meglumine antimoniate by EV route at 20mg/kg/day, for 20 days.
  arm group label: Tofacitinib and Sbv
  arm group type: Experimental
  description: Eleven CL patients will receive oral tofatinib (10mg daily for 30 days) associated to meglumine antimoniate by EV route at 20mg/kg/day, for 20 days.
  intervention type: Drug
  intervention name: Oral tofacitinib
  description: Association of tofacitinib and meglumine antimoniate
  arm group label: Tofacitinib and Sbv
  intervention type: Drug
  intervention name: Parenteral meglumine antimoniate
  description: Meglumine antimoniate
  arm group label: Placebo and Sbv
  arm group label: Tofacitinib and Sbv
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 60 Years
  healthy volunteers: No
  last name: EDGAR CARVALHO, MD, PhD
  role: Principal Investigator
  affiliation: Federal University of Bahia
  last name: EDGAR L CARVALHO, MD, PhD
  phone: 7132377353
  email: imuno@ufba.br
  last name: PAULO R LIMA MACHADO, MD, PhD
  phone: 7132377353
  email: 19pmachado@gmail.com
  facility: 
  country: Brazil
  responsible party type: Principal Investigator
  investigator affiliation: Hospital Universitário Professor Edgard Santos
  investigator full name: Paulo Roberto Lima Machado
  investigator title: Senior Researcher
  mesh term: Leishmaniasis
  mesh term: Leishmaniasis, Cutaneous
  mesh term: Meglumine Antimoniate
  mesh term: Tofacitinib
  sharing ipd: No
  ipd description: There is not a plan to make IPD available.