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/NCT06041620</url>
    </required_header>
    <id_info>
      <org_study_id>VGB-Ex01-001</org_study_id>
      <nct_id>NCT06041620</nct_id>
    </id_info>
    <brief_title>Safety and Efficacy Evaluation of Autologous CRISPR-Cas12b Edited Hematopoietic Stem Cells</brief_title>
    <official_title>A Study to Evaluate the Efficacy and Safety of Autologous CRISPR-Cas12b Edited Hematopoietic Stem Cells in Transfusion-dependent β Thalassemia Patients</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Institute of Hematology &amp; Blood Diseases Hospital, China</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Shanghai Vitalgen BioPharma Co., Ltd.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Institute of Hematology &amp; Blood Diseases Hospital, China</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>
        This is a single-arm, open, single-injection exploratory clinical study with two&#xD;
        transfusion-dependent β thalassemia (β-TDT) participants planned to enroll.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Through CRISPR-Cas 12b editing tool with independent intellectual property rights of Chinese&#xD;
        Academy of Sciences, HBG1/2 promoter was edited to reactivate gamma-globin and induce fetal&#xD;
        hemoglobin (HbF) expression. This leads to a subsequent reduction in ineffective red blood&#xD;
        cell production (due to a reduction in the uncompounded alpha-globin chain) and improved red&#xD;
        blood cell survival (due to reduced hemolysis), ultimately improving the sequelae of anemia&#xD;
        and reducing the need for transfusion. Safety and efficacy will be evaluated continuously&#xD;
        throughout the study, follow-up was up to 24 months. After the end of this trial,&#xD;
        participants who received the infusion of autologous CRISPR-Cas12b edited hematopoietic stem&#xD;
        cells (VGB-Ex01) will be invited to participate in the long-term follow-up study to complete&#xD;
        the 15-year follow-up plan.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 15, 2023</start_date>
    <completion_date type="Anticipated">June 30, 2026</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2025</primary_completion_date>
    <phase>N/A</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>Incidence of adverse events and serious adverse events</measure>
      <time_frame>Baseline up to 24 months</time_frame>
      <description>An adverse event is any untoward medical occurrence in a clinical investigation/participant administered a product; the event will not need to have a causal relationship with the treatment. A serious adverse event is any untoward medical occurrence at any dose that resulted in death; life threatening;require inpatient hospitalization or prolongation of existing hospitalization; result in persistent or significant disability/incapacity; result in congenital anomaly/birth defect.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of subjects with neutrophil implantation ≤ 42 days</measure>
      <time_frame>Baseline up to 42 days</time_frame>
      <description>Neutrophil implantation was defined as 3 consecutive days with 3 tests for ANC≥500/μL.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Number of subjects transfusion independence (TI) for at least 6 months after transfusion</measure>
      <time_frame>Baseline up to 6 months</time_frame>
      <description>TI defined as Hb≥9g/dL without red blood cell infusion</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of subjects transfusion independence (TI) for at least 12 months after transfusion</measure>
      <time_frame>Baseline up to 12 months</time_frame>
      <description>TI defined as Hb≥9g/dL without red blood cell infusion</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Fetal hemoglobin (HbF) concentration</measure>
      <time_frame>Baseline up to 24 months</time_frame>
      <description>Changes in HbF concentration from baseline after transfusion</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Total hemoglobin (Hb) concentration</measure>
      <time_frame>Baseline up to 24 months</time_frame>
      <description>Changes in Hb concentration compared with baseline after transfusion</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The proportion of circulating red blood cells</measure>
      <time_frame>Baseline up to 24 months</time_frame>
      <description>Changes in the proportion of circulating red blood cells expressing fetal hemoglobin compared to baseline</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">2</enrollment>
    <condition>Thalassemia, Beta</condition>
    <condition>Thalassemia Major</condition>
    <arm_group>
      <arm_group_label>VGB-Ex01</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Each subject will accept one dose of VGB-Ex01.</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>VGB-Ex01</intervention_name>
      <description>CRISPR-Cas12b editing hematopoietic stem cells</description>
      <arm_group_label>VGB-Ex01</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age 3-35 years old (inclusive), male or female;&#xD;
  &#xD;
            -  The subject and/or his/her legally recognized representative/parent/guardian fully&#xD;
               understands the study and all information related to the study and has signed the&#xD;
               informed consent form;&#xD;
  &#xD;
            -  Clinical diagnosis of transfusion-dependent β-thalassemia (TDT) with a blood&#xD;
               transfusion record within 2 years (inclusive) prior to screening showing a history of&#xD;
               ≥ 10 units (U)/kg/year (or ≥ 100 mL/kg/year) or ≥ 8 times/year of suspended RBC&#xD;
               transfusions in at least 1 consecutive 12-month period;&#xD;
  &#xD;
            -  Karnofsky score (for subjects aged ≥ 16 years) or Lansky score (for subjects aged &lt; 16&#xD;
               years) of ≥ 80;&#xD;
  &#xD;
            -  Subjects in stable disease state who are eligible for hematopoietic stem cell&#xD;
               transplantation as per investigator's judgment;&#xD;
  &#xD;
            -  Access to diagnosis and treatment records issued by medical professional institutions&#xD;
               within 2 years prior to screening, including the records of blood transfusions,&#xD;
               hematology, serum chemistry, and other examinations;&#xD;
  &#xD;
            -  Willing and able to comply with study procedures, with good compliance, and willing to&#xD;
               receive and complete the follow-up study with a duration of at least 2 years;&#xD;
  &#xD;
            -  Subjects of childbearing potential (including female subjects of childbearing&#xD;
               potential and male subjects whose partners are of childbearing potential) must use&#xD;
               effective contraception within 12 months of treatment.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Diagnosis of associated α-thalassemia: &gt; 1 alpha chain deletion or alpha gene&#xD;
               functional defect;&#xD;
  &#xD;
            -  Have available HLA-fully matched donors and acceptable for allogeneic hematopoietic&#xD;
               stem cell transplantation;&#xD;
  &#xD;
            -  Irregular antibody or platelet antibody positive;&#xD;
  &#xD;
            -  Prior allogeneic bone marrow transplantation or gene therapy;&#xD;
  &#xD;
            -  Subjects with clinically significant and active bacterial, viral, fungal, or parasitic&#xD;
               infection as determined by the investigator at screening, including but not limited to&#xD;
               those with positive etiology of human immunodeficiency virus (HIV-1/2), human&#xD;
               cytomegalovirus (HCMV-DNA), Epstein-Barr virus (EBV-DNA), or Treponema pallidum&#xD;
               antibody (TP-Ab), or with previous hepatitis B or C infection;&#xD;
  &#xD;
            -  Subjects with an injury of major organs&#xD;
  &#xD;
            -  Contraindications for hematopoietic stem cell collection and poor collection&#xD;
               efficiency judged by the investigator;&#xD;
  &#xD;
            -  Contraindications to the clinical investigational product and its excipients, G-CSF&#xD;
               (hematopoietic stem cell mobilization), plerixafor (hematopoietic stem cell&#xD;
               mobilization), busulfan (myeloablation), and other drugs;&#xD;
  &#xD;
            -  Participation within 3 months prior to screening or current participation in another&#xD;
               interventional clinical study;&#xD;
  &#xD;
            -  History or family history of malignancy or myeloproliferative disorder;&#xD;
  &#xD;
            -  History of uncontrollable epilepsy, mental disorder, or other psychiatric disorders;&#xD;
  &#xD;
            -  Abuse of psychoactive substance, drug, or alcohol within 6 months prior to enrollment;&#xD;
  &#xD;
            -  Pregnant or breastfeeding females;&#xD;
  &#xD;
            -  Other diseases or reasons that interfere with study procedures;&#xD;
  &#xD;
            -  Any other conditions that the investigator deems unsuitable for the subject's&#xD;
               participation in the study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>3 Years</minimum_age>
      <maximum_age>35 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Jun Shi, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Institute of Hematology &amp; Blood Diseases Hospital, China</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Jun Shi, PhD</last_name>
      <phone>13752253515</phone>
      <email>shijun@ihcams.ac.cn</email>
    </overall_contact>
    <location>
      <facility>
        <name>Regenerative Medicine Center</name>
        <address>
          <city>Tianjin</city>
          <state>Tianjin</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 11, 2023</study_first_submitted>
    <study_first_submitted_qc>September 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 18, 2023</study_first_posted>
    <last_update_submitted>September 11, 2023</last_update_submitted>
    <last_update_submitted_qc>September 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Institute of Hematology &amp; Blood Diseases Hospital, China</investigator_affiliation>
      <investigator_full_name>Jun Shi</investigator_full_name>
      <investigator_title>Director of Regenerative Medical Center</investigator_title>
    </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>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </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/NCT06041620
  org study id: VGB-Ex01-001
  nct id: NCT06041620
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This is a single-arm, open, single-injection exploratory clinical study with two
        transfusion-dependent β thalassemia (β-TDT) participants planned to enroll.
  Through CRISPR-Cas 12b editing tool with independent intellectual property rights of Chinese
        Academy of Sciences, HBG1/2 promoter was edited to reactivate gamma-globin and induce fetal
        hemoglobin (HbF) expression. This leads to a subsequent reduction in ineffective red blood
        cell production (due to a reduction in the uncompounded alpha-globin chain) and improved red
        blood cell survival (due to reduced hemolysis), ultimately improving the sequelae of anemia
        and reducing the need for transfusion. Safety and efficacy will be evaluated continuously
        throughout the study, follow-up was up to 24 months. After the end of this trial,
        participants who received the infusion of autologous CRISPR-Cas12b edited hematopoietic stem
        cells (VGB-Ex01) will be invited to participate in the long-term follow-up study to complete
        the 15-year follow-up plan.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence of adverse events and serious adverse events
  time frame: Baseline up to 24 months
  description: An adverse event is any untoward medical occurrence in a clinical investigation/participant administered a product; the event will not need to have a causal relationship with the treatment. A serious adverse event is any untoward medical occurrence at any dose that resulted in death; life threatening;require inpatient hospitalization or prolongation of existing hospitalization; result in persistent or significant disability/incapacity; result in congenital anomaly/birth defect.
  measure: Number of subjects with neutrophil implantation ≤ 42 days
  time frame: Baseline up to 42 days
  description: Neutrophil implantation was defined as 3 consecutive days with 3 tests for ANC≥500/μL.
  measure: Number of subjects transfusion independence (TI) for at least 6 months after transfusion
  time frame: Baseline up to 6 months
  description: TI defined as Hb≥9g/dL without red blood cell infusion
  measure: Number of subjects transfusion independence (TI) for at least 12 months after transfusion
  time frame: Baseline up to 12 months
  description: TI defined as Hb≥9g/dL without red blood cell infusion
  measure: Fetal hemoglobin (HbF) concentration
  time frame: Baseline up to 24 months
  description: Changes in HbF concentration from baseline after transfusion
  measure: Total hemoglobin (Hb) concentration
  time frame: Baseline up to 24 months
  description: Changes in Hb concentration compared with baseline after transfusion
  measure: The proportion of circulating red blood cells
  time frame: Baseline up to 24 months
  description: Changes in the proportion of circulating red blood cells expressing fetal hemoglobin compared to baseline
  arm group label: VGB-Ex01
  arm group type: Experimental
  description: Each subject will accept one dose of VGB-Ex01.
  intervention type: Biological
  intervention name: VGB-Ex01
  description: CRISPR-Cas12b editing hematopoietic stem cells
  arm group label: VGB-Ex01
  criteria: 
  gender: All
  minimum age: 3 Years
  maximum age: 35 Years
  healthy volunteers: No
  last name: Jun Shi, PhD
  role: Principal Investigator
  affiliation: Institute of Hematology & Blood Diseases Hospital, China
  last name: Jun Shi, PhD
  phone: 13752253515
  email: shijun@ihcams.ac.cn
  facility: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Institute of Hematology & Blood Diseases Hospital, China
  investigator full name: Jun Shi
  investigator title: Director of Regenerative Medical Center
  mesh term: Thalassemia
  mesh term: beta-Thalassemia
  sharing ipd: No