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/NCT06009965</url>
    </required_header>
    <id_info>
      <org_study_id>SN-01</org_study_id>
      <nct_id>NCT06009965</nct_id>
    </id_info>
    <brief_title>Efficacy of IST Combined With TPO-RA in the Treatment of AA and Establishment of a Recurrence Prediction System</brief_title>
    <official_title>Establishment of an Efficacy and Relapse Prediction System for Immunosuppressants Combined With Thrombopoietin Receptor Agonists in the Treatment of Aplastic Anemia</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Peking Union Medical College Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Peking Union Medical College Hospital</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        In this study, investigators intend to prospectively study treatment-naive AA patients&#xD;
        (including SAA and NSAA) who are non-transplant candidates in northern China. Patients with&#xD;
        SAA receive ATG+CsA+Herombopag, and patients with NSAA receive CsA+ Herombopag. Investigators&#xD;
        explored possible indicators of participants' predictive efficacy and built predictive&#xD;
        models. After the participants achieved response, they used a tapering regimen, observed&#xD;
        relapse and clonal evolution, and developed a predictive model of relapse.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        1) Patients in the SAA group: CsA: 3-5mg/kg/day, monitor the trough concentration every&#xD;
        month, and maintain the trough concentration at 100-200ng/ml. ATG: rabbit anti-thymocyte&#xD;
        immunoglobulin (r-ATG) 3mg/kg/d×5 days, or porcine anti-lymphocyte immunoglobulin ((p-ATG)&#xD;
        25mg/kg/d×5 days; TPO-RA: Herombopag starts at 7.5 mg qd, monitor the blood picture every 2&#xD;
        weeks, if the effect is not good, add 1 tablet every 2 weeks, up to 6 tablets (15 mg) qd.&#xD;
  &#xD;
        Patients in the NSAA group: CsA: 3-5mg/kg/day, monitor the trough concentration every month,&#xD;
        and maintain the trough concentration at 100-200ng/ml. TPO-RA: start with 7.5mg qd of&#xD;
        Herombopag, monitor the blood picture every 2 weeks, if the effect is not good, add 1 tablet&#xD;
        every 2 weeks, up to 6 tablets (15mg) qd.&#xD;
  &#xD;
        (2) Those who are effective after 6 months of treatment continue to receive sufficient CsA&#xD;
        treatment for at least 1.5 years, and then slowly reduce the dose until the end of the&#xD;
        reduction. Those who fail to withdraw from the clinical trial.&#xD;
  &#xD;
        (3) Participants who achieve CR or PR after treatment, but when the curative effect does not&#xD;
        increase after 3 months of maintenance treatment, start to reduce the dose of Herombopag, and&#xD;
        reduce one tablet every 3 months until the reduction stops. If recurrence occurs, recover Up&#xD;
        to the last dose or even increase the dose, after reaching the best curative effect, reduce&#xD;
        one tablet every 3 months until the reduction stops, and those who cannot recover are defined&#xD;
        as relapse.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">January 20, 2023</start_date>
    <completion_date type="Anticipated">January 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">January 30, 2025</primary_completion_date>
    <phase>Phase 4</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Overall response rate</measure>
      <time_frame>24 weeks after treatment</time_frame>
      <description>Overall response rate</description>
    </primary_outcome>
    <primary_outcome>
      <measure>24-month recurrence rate</measure>
      <time_frame>96 weeks after treatment</time_frame>
      <description>.24-month recurrence rate</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall response rate</measure>
      <time_frame>56 weeks after treatment</time_frame>
      <description>Overall response rate</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>36-month recurrence rate</measure>
      <time_frame>144 weeks after treatment</time_frame>
      <description>36-month recurrence rate</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">210</enrollment>
    <condition>Aplastic Anemia</condition>
    <condition>CSA</condition>
    <condition>Drug Therapy</condition>
    <arm_group>
      <arm_group_label>Severe aplastic anemia group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>CsA: 3-5 mg/kg/day, monitor trough concentration monthly, maintain trough concentration at 100-200 ng/ml.ATG: rabbit anti-thymocyte immunoglobulin (r-ATG) 3 mg/kg/d x 5 days or porcine anti-lymphocyte immunoglobulin ((p-ATG) 25 mg/kg/d x 5 days.TPO-RA: Heptapepto-Papa 7.5 mg qd to start. Monitor blood every 2 weeks and if ineffective, increase by 1 tablet every 2 weeks up to a maximum of 6 tablets (15mg) qd.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Non-severe aplastic anemia group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>CsA: 3-5 mg/kg/day, monitor trough concentrations monthly, maintain trough concentrations at 100-200 ng/ml.TPO-RA: Start with Hetropoxyphene 7.5 mg qd, monitor blood every 2 weeks, and if ineffective, increase by 1 tablet every 2 weeks up to a maximum of 6 tablets (15 mg) qd.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>CsA+ATG+Herombopag</intervention_name>
      <description>CsA: 3-5 mg/kg/day, monitor trough concentration monthly, maintain trough concentration at 100-200 ng/ml.ATG: rabbit anti-thymocyte immunoglobulin (r-ATG) 3 mg/kg/d x 5 days or porcine anti-lymphocyte immunoglobulin ((p-ATG) 25 mg/kg/d x 5 days.TPO-RA: Heptapepto-Papa 7.5 mg qd to start. Monitor blood every 2 weeks and if ineffective, increase by 1 tablet every 2 weeks up to a maximum of 6 tablets (15mg) qd.</description>
      <arm_group_label>Severe aplastic anemia group</arm_group_label>
      <other_name>SAA group intervention treatment</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>CsA+Herombopag</intervention_name>
      <description>CsA: 3-5 mg/kg/day, monitor trough concentrations monthly, maintain trough concentrations at 100-200 ng/ml.TPO-RA: Start with Hetropoxyphene 7.5 mg qd, monitor blood every 2 weeks, and if ineffective, increase by 1 tablet every 2 weeks up to a maximum of 6 tablets (15 mg) qd.</description>
      <arm_group_label>Non-severe aplastic anemia group</arm_group_label>
      <other_name>NSAA group intervention treatment</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age: 18-75 years old, gender is not limited&#xD;
  &#xD;
            2. Definite diagnosis of AA&#xD;
  &#xD;
            3. No HSCT indication or unconditional HSCT&#xD;
  &#xD;
            4. SAA/VSAA patients were willing to accept ATG+CsA+TPO-RA treatment, NSAA was willing to&#xD;
               accept CsA+TPO-RA treatment, and were willing to follow up regularly&#xD;
  &#xD;
            5. Baseline serum transaminase, total bilirubin and serum creatinine were less than 1.5&#xD;
               times the normal value&#xD;
  &#xD;
            6. Baseline liver and kidney function was less than 1.5 times the normal value&#xD;
  &#xD;
            7. Eastern Cancer Cooperation Group (ECOG) score status 0-2&#xD;
  &#xD;
            8. Agree to sign the consent form&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Congenital AA&#xD;
  &#xD;
            2. Cytogenetic evidence of clonal hematologic bone marrow disease&#xD;
  &#xD;
            3. PNH clone ≥50%&#xD;
  &#xD;
            4. Allergic to ATG, cyclosporine and hexapopal in the past&#xD;
  &#xD;
            5. Uncontrolled infection or bleeding at enrollment&#xD;
  &#xD;
            6. Received hematopoietic stem cell transplantation (HSCT) before enrollment&#xD;
  &#xD;
            7. Any concomitant malignancy within 5 years, except for local skin basal cell carcinoma&#xD;
  &#xD;
            8. A history of thromboembolic events, myocardial infarction, or stroke (including&#xD;
               antiphospholipid antibody syndrome); Currently using anticoagulants&#xD;
  &#xD;
            9. Pregnant or lactating women&#xD;
  &#xD;
           10. Situations considered unsuitable for clinical research by other researchers&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Bing Bing, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Peking Union Medical College Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Yali Du, Master</last_name>
      <phone>+8615845992396</phone>
      <email>yali_crazy@126.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Peking union medical college hospital</name>
        <address>
          <city>Beijing</city>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Bing Han, Doctor</last_name>
        <phone>+86-010-69155760</phone>
        <email>hanbingtg123@163.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 6, 2023</study_first_submitted>
    <study_first_submitted_qc>August 20, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 24, 2023</study_first_posted>
    <last_update_submitted>August 20, 2023</last_update_submitted>
    <last_update_submitted_qc>August 20, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 24, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Peking Union Medical College Hospital</investigator_affiliation>
      <investigator_full_name>Bing Han</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <keyword>Aplastic Anemia</keyword>
    <keyword>CsA</keyword>
    <keyword>ATG</keyword>
    <keyword>TPO-RA</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Anemia</mesh_term>
      <mesh_term>Anemia, Aplastic</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>individual participant data would be accepted upon request</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
      <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
      <ipd_time_frame>10 years</ipd_time_frame>
      <ipd_access_criteria>email request</ipd_access_criteria>
    </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/NCT06009965
  org study id: SN-01
  nct id: NCT06009965
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  In this study, investigators intend to prospectively study treatment-naive AA patients
        (including SAA and NSAA) who are non-transplant candidates in northern China. Patients with
        SAA receive ATG+CsA+Herombopag, and patients with NSAA receive CsA+ Herombopag. Investigators
        explored possible indicators of participants' predictive efficacy and built predictive
        models. After the participants achieved response, they used a tapering regimen, observed
        relapse and clonal evolution, and developed a predictive model of relapse.
  1) Patients in the SAA group: CsA: 3-5mg/kg/day, monitor the trough concentration every
        month, and maintain the trough concentration at 100-200ng/ml. ATG: rabbit anti-thymocyte
        immunoglobulin (r-ATG) 3mg/kg/d×5 days, or porcine anti-lymphocyte immunoglobulin ((p-ATG)
        25mg/kg/d×5 days; TPO-RA: Herombopag starts at 7.5 mg qd, monitor the blood picture every 2
        weeks, if the effect is not good, add 1 tablet every 2 weeks, up to 6 tablets (15 mg) qd.
  
        Patients in the NSAA group: CsA: 3-5mg/kg/day, monitor the trough concentration every month,
        and maintain the trough concentration at 100-200ng/ml. TPO-RA: start with 7.5mg qd of
        Herombopag, monitor the blood picture every 2 weeks, if the effect is not good, add 1 tablet
        every 2 weeks, up to 6 tablets (15mg) qd.
  
        (2) Those who are effective after 6 months of treatment continue to receive sufficient CsA
        treatment for at least 1.5 years, and then slowly reduce the dose until the end of the
        reduction. Those who fail to withdraw from the clinical trial.
  
        (3) Participants who achieve CR or PR after treatment, but when the curative effect does not
        increase after 3 months of maintenance treatment, start to reduce the dose of Herombopag, and
        reduce one tablet every 3 months until the reduction stops. If recurrence occurs, recover Up
        to the last dose or even increase the dose, after reaching the best curative effect, reduce
        one tablet every 3 months until the reduction stops, and those who cannot recover are defined
        as relapse.
  allocation: Non-Randomized
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Overall response rate
  time frame: 24 weeks after treatment
  description: Overall response rate
  measure: 24-month recurrence rate
  time frame: 96 weeks after treatment
  description: .24-month recurrence rate
  measure: Overall response rate
  time frame: 56 weeks after treatment
  description: Overall response rate
  measure: 36-month recurrence rate
  time frame: 144 weeks after treatment
  description: 36-month recurrence rate
  arm group label: Severe aplastic anemia group
  arm group type: Experimental
  description: CsA: 3-5 mg/kg/day, monitor trough concentration monthly, maintain trough concentration at 100-200 ng/ml.ATG: rabbit anti-thymocyte immunoglobulin (r-ATG) 3 mg/kg/d x 5 days or porcine anti-lymphocyte immunoglobulin ((p-ATG) 25 mg/kg/d x 5 days.TPO-RA: Heptapepto-Papa 7.5 mg qd to start. Monitor blood every 2 weeks and if ineffective, increase by 1 tablet every 2 weeks up to a maximum of 6 tablets (15mg) qd.
  arm group label: Non-severe aplastic anemia group
  arm group type: Experimental
  description: CsA: 3-5 mg/kg/day, monitor trough concentrations monthly, maintain trough concentrations at 100-200 ng/ml.TPO-RA: Start with Hetropoxyphene 7.5 mg qd, monitor blood every 2 weeks, and if ineffective, increase by 1 tablet every 2 weeks up to a maximum of 6 tablets (15 mg) qd.
  intervention type: Drug
  intervention name: CsA+ATG+Herombopag
  description: CsA: 3-5 mg/kg/day, monitor trough concentration monthly, maintain trough concentration at 100-200 ng/ml.ATG: rabbit anti-thymocyte immunoglobulin (r-ATG) 3 mg/kg/d x 5 days or porcine anti-lymphocyte immunoglobulin ((p-ATG) 25 mg/kg/d x 5 days.TPO-RA: Heptapepto-Papa 7.5 mg qd to start. Monitor blood every 2 weeks and if ineffective, increase by 1 tablet every 2 weeks up to a maximum of 6 tablets (15mg) qd.
  arm group label: Severe aplastic anemia group
  other name: SAA group intervention treatment
  intervention type: Drug
  intervention name: CsA+Herombopag
  description: CsA: 3-5 mg/kg/day, monitor trough concentrations monthly, maintain trough concentrations at 100-200 ng/ml.TPO-RA: Start with Hetropoxyphene 7.5 mg qd, monitor blood every 2 weeks, and if ineffective, increase by 1 tablet every 2 weeks up to a maximum of 6 tablets (15 mg) qd.
  arm group label: Non-severe aplastic anemia group
  other name: NSAA group intervention treatment
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Bing Bing, PhD
  role: Principal Investigator
  affiliation: Peking Union Medical College Hospital
  last name: Yali Du, Master
  phone: +8615845992396
  email: yali_crazy@126.com
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Peking Union Medical College Hospital
  investigator full name: Bing Han
  investigator title: Professor
  mesh term: Anemia
  mesh term: Anemia, Aplastic
  sharing ipd: Yes
  ipd description: individual participant data would be accepted upon request
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Informed Consent Form (ICF)
  ipd info type: Clinical Study Report (CSR)
  ipd time frame: 10 years
  ipd access criteria: email request