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/NCT06024876</url>
    </required_header>
    <id_info>
      <org_study_id>CS-101-06</org_study_id>
      <nct_id>NCT06024876</nct_id>
    </id_info>
    <brief_title>A Clinical Study Evaluating the Safety and Efficacy of CS-101 in Treating Subjects With β-thalassemia</brief_title>
    <official_title>A Clinical Study Evaluating the Safety and Efficacy of In-vitro tBE Edited Autologous Hematopoietic Stem Progenitor Cells(CS-101) in Treating Subjects With β-thalassemia</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>CorrectSequence Therapeutics Co., Ltd</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>First Affiliated Hospital of Guangxi Medical University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>CorrectSequence Therapeutics Co., Ltd</source>
    <oversight_info>
      <has_dmc>No</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>
        The goal of this open label, single-arm clinical study is to learn about the safety and&#xD;
        efficacy of CS-101 in treating β-thalassemia.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        CS-101 is an autologous CD34+ cell suspension, edited by in vitro base editing technology,&#xD;
        which modifies the BCL11A binding site in HBG promoter, so that it loses the ability to bind&#xD;
        to BCL11A, which can re-induce the production of γ-globin chain and increase the&#xD;
        concentration of fetal hemoglobin(HbF) in the blood, compensating for the function of missing&#xD;
        adult hemoglobin HbA to achieve clinical cure. The therapy addresses two major challenges in&#xD;
        the current treatment of the disease: lack of matching donors and graft-versus-host diseases&#xD;
        in allogeneic hematopoietic stem cell transplantation.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 26, 2023</start_date>
    <completion_date type="Anticipated">June 30, 2025</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2024</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>Frequency and severity of adverse events(AEs）as assessed by CTCAE v5.0</measure>
      <time_frame>From signing informed consent to 12 months post-CS-101 infusion</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Time to neutrophil and platelet engraftment</measure>
      <time_frame>Days post-CS-101 infusion</time_frame>
      <description>Time to neutrophil engraftment is defined as first day of 3 consecutive measurements of absolute neutrophil count≥0.5×10^9/L on three different days； Time to platelet engraftment is defined as first day of 3 consecutive measurements of absolute platelet count≥20×10^9/L on three different days and without platelet transfusion；</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Proportion of subjects with engraftment</measure>
      <time_frame>within 42 days post-CS-101infusion</time_frame>
      <description>Subjects with engraftment is defined as neutrophil engrafted</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Incidence of transplant-related mortality</measure>
      <time_frame>From baseline to 100 days post-CS-101 infusion</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>All-cause mortality</measure>
      <time_frame>From signing informed consent to 12 months post-CS-101 infusion</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Proportion of subjects achieving transfusion independence for at least 6 consecutive months</measure>
      <time_frame>From 3 months up to 12 months post-CS-101 infusion</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Time to last red blood cell(RBC) transfusion</measure>
      <time_frame>Days post-CS-101 infusion</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in total hemoglobin(Hb) concentration over time</measure>
      <time_frame>up to 12 months post-CS-101 infusion</time_frame>
      <description>Total hemoglobin concentration change from baseline to 12 months post-CS-101 infusion</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in fetal hemoglobin(HbF) concentration over time</measure>
      <time_frame>up to 12 months post-CS-101 infusion</time_frame>
      <description>γ-globin concentration change from baseline to 12 months post-CS-101 infusion</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Chimerism level in Peripheral blood and bone marrow</measure>
      <time_frame>up to 12 months post-CS-101 infusion</time_frame>
      <description>Proportion of alleles with intended genetic modification in peripheral blood leukocytes and bone marrow over time</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">5</enrollment>
    <condition>Beta-Thalassemia</condition>
    <arm_group>
      <arm_group_label>CS-101</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>CS-101: Autologous CD34+ hematopoietic stem cell suspension modified by in vitro base editing technique</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>CS-101</intervention_name>
      <description>Autologous CD34+ hematopoietic stem cell suspension modified by in vitro base editing technique</description>
      <arm_group_label>CS-101</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Key Inclusion Criteria：&#xD;
  &#xD;
            -  6 to 35 years old(inclusive) male or female subjects at the time of informed&#xD;
               consenting&#xD;
  &#xD;
            -  Diagnosis of β-thalassemia, genotypes include but are not limited to β+β0，βEβ0，β0β0,&#xD;
               etc&#xD;
  &#xD;
            -  History of at least≥8 units/year of packed RBC transfusions in the prior 12 months&#xD;
               prior to the screening period&#xD;
  &#xD;
            -  Generally in good condition, Karnofsky performance score≥60 points for subjects≥16&#xD;
               years old at the time of autologous hematopoietic stem cell collection, or Lansky&#xD;
               Play-Performance score≥60 points for subjects under 16 years old, or equivalent&#xD;
               clinical evaluation as the investigator site's common practice&#xD;
  &#xD;
          Key Exclusion Criteria:&#xD;
  &#xD;
            -  Treatment with other investigational medications or other experimental interventions&#xD;
               30 days prior to signing informed consent or within 6 half-lives of the drug,&#xD;
               whichever is longer.&#xD;
  &#xD;
            -  Subjects who have received or are receiving thalidomide and/or Luspatercept, when&#xD;
               their drug-drug interaction on the efficacy and safety of CS-101 cannot be ruled out,&#xD;
               unless at least there are 3 test results showing the total hemoglobin level before&#xD;
               transfusion is below 9g/dL in the past 6 months before screening.&#xD;
  &#xD;
            -  Previously received allogeneic hematopoietic stem cell transplantation or gene(edited)&#xD;
               therapy.&#xD;
  &#xD;
            -  Subjects have available related fully matching donors and are eligible and prepared&#xD;
               for allogeneic hematopoietic stem cell transplantation.&#xD;
  &#xD;
            -  Those with active infections, including but not limited to: HIV, hepatitis B,&#xD;
               hepatitis C, cytomegalovirus, Epstein-Barr virus and treponema pallidum test positive,&#xD;
               or known tuberculosis, parasitic infection, etc. who are judged by the investigator to&#xD;
               be unsuitable to participate in this study.&#xD;
  &#xD;
            -  Echocardiography results with ejection fraction below 45%.&#xD;
  &#xD;
            -  Advanced liver disease, defined as：&#xD;
  &#xD;
          Aspartate aminotransferase (AST), alanine aminotransferase (ALT) &gt;3 × upper limit of normal&#xD;
          (ULN) or:&#xD;
  &#xD;
          Baseline International Normalized Ratio (INR) &gt;1.5 × ULN.&#xD;
  &#xD;
            -  MRI during the screening period showed heavy iron overload and is judged by the&#xD;
               investigator to be unable to participate in the study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>6 Years</minimum_age>
      <maximum_age>35 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Yongrong Lai, M.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>First Affiliated Hospital of Guangxi Medical University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Yaliang Li</last_name>
      <phone>+8619514612757</phone>
      <email>yaliang.li@correctsequence.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>The First Affiliated Hospital of Guangxi Medical University</name>
        <address>
          <city>Nanning</city>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Yongrong Lai, MD</last_name>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 23, 2023</study_first_submitted>
    <study_first_submitted_qc>August 29, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 6, 2023</study_first_posted>
    <last_update_submitted>September 9, 2023</last_update_submitted>
    <last_update_submitted_qc>September 9, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Thalassemia</mesh_term>
      <mesh_term>beta-Thalassemia</mesh_term>
    </condition_browse>
    <!-- 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/NCT06024876
  org study id: CS-101-06
  nct id: NCT06024876
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this open label, single-arm clinical study is to learn about the safety and
        efficacy of CS-101 in treating β-thalassemia.
  CS-101 is an autologous CD34+ cell suspension, edited by in vitro base editing technology,
        which modifies the BCL11A binding site in HBG promoter, so that it loses the ability to bind
        to BCL11A, which can re-induce the production of γ-globin chain and increase the
        concentration of fetal hemoglobin(HbF) in the blood, compensating for the function of missing
        adult hemoglobin HbA to achieve clinical cure. The therapy addresses two major challenges in
        the current treatment of the disease: lack of matching donors and graft-versus-host diseases
        in allogeneic hematopoietic stem cell transplantation.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Frequency and severity of adverse events(AEs）as assessed by CTCAE v5.0
  time frame: From signing informed consent to 12 months post-CS-101 infusion
  measure: Time to neutrophil and platelet engraftment
  time frame: Days post-CS-101 infusion
  description: Time to neutrophil engraftment is defined as first day of 3 consecutive measurements of absolute neutrophil count≥0.5×10^9/L on three different days； Time to platelet engraftment is defined as first day of 3 consecutive measurements of absolute platelet count≥20×10^9/L on three different days and without platelet transfusion；
  measure: Proportion of subjects with engraftment
  time frame: within 42 days post-CS-101infusion
  description: Subjects with engraftment is defined as neutrophil engrafted
  measure: Incidence of transplant-related mortality
  time frame: From baseline to 100 days post-CS-101 infusion
  measure: All-cause mortality
  time frame: From signing informed consent to 12 months post-CS-101 infusion
  measure: Proportion of subjects achieving transfusion independence for at least 6 consecutive months
  time frame: From 3 months up to 12 months post-CS-101 infusion
  measure: Time to last red blood cell(RBC) transfusion
  time frame: Days post-CS-101 infusion
  measure: Change in total hemoglobin(Hb) concentration over time
  time frame: up to 12 months post-CS-101 infusion
  description: Total hemoglobin concentration change from baseline to 12 months post-CS-101 infusion
  measure: Change in fetal hemoglobin(HbF) concentration over time
  time frame: up to 12 months post-CS-101 infusion
  description: γ-globin concentration change from baseline to 12 months post-CS-101 infusion
  measure: Chimerism level in Peripheral blood and bone marrow
  time frame: up to 12 months post-CS-101 infusion
  description: Proportion of alleles with intended genetic modification in peripheral blood leukocytes and bone marrow over time
  arm group label: CS-101
  arm group type: Experimental
  description: CS-101: Autologous CD34+ hematopoietic stem cell suspension modified by in vitro base editing technique
  intervention type: Biological
  intervention name: CS-101
  description: Autologous CD34+ hematopoietic stem cell suspension modified by in vitro base editing technique
  arm group label: CS-101
  criteria: 
  gender: All
  minimum age: 6 Years
  maximum age: 35 Years
  healthy volunteers: No
  last name: Yongrong Lai, M.D.
  role: Principal Investigator
  affiliation: First Affiliated Hospital of Guangxi Medical University
  last name: Yaliang Li
  phone: +8619514612757
  email: yaliang.li@correctsequence.com
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Thalassemia
  mesh term: beta-Thalassemia