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/NCT05988216</url>
    </required_header>
    <id_info>
      <org_study_id>2022-BRL-301A-SLE-IIT</org_study_id>
      <nct_id>NCT05988216</nct_id>
    </id_info>
    <brief_title>Universal CAR-T Cells (BRL-301) in Refractory Systemic Lupus Erythematosus</brief_title>
    <official_title>A Clinical Study on the Safety and Efficacy of BRL-301 (Allogeneic Chimeric Antigen Receptor T Cell Injection Targeting CD19 Gene) in the Treatment of Refractory Systemic Lupus Erythematosus</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Bioray Laboratories</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>First Affiliated Hospital of Zhejiang University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Bioray Laboratories</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>
        This is an investigator initiated trial to assess the efficacy and safety of BRL-301 in the&#xD;
        refractory systemic lupus erythematosus.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The study had the following sequential phases: Screening, Pre-Treatment (Cell Product&#xD;
        Preparation &amp; Lymphodepleting Chemotherapy), Treatment and Follow-up.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">September 2025</completion_date>
    <primary_completion_date type="Anticipated">December 2024</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>The safety of BRL-301 in refractory systemic lupus erythematosus</measure>
      <time_frame>12 months</time_frame>
      <description>Incidence and severity of AEs and SAEs, including changes in laboratory values, ECG and vital signs as assessed by CTCAE v5.0.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>The efficiency of BRL-301 in refractory systemic lupus erythematosus</measure>
      <time_frame>3 months</time_frame>
      <description>Number of patients with SRI-4 response: including SELENA-SLEDAI ≥4-Point improvement, BILAG 2004 with No new A domain score AND no more than 1 new B domain scores, PGA with No worsening (&lt;0.3-point increase)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cellular kinetics</measure>
      <time_frame>12 months</time_frame>
      <description>CAR transgene levels by quantitative polymerase chain reaction (qPCR) in peripheral blood</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">12</enrollment>
    <condition>Systemic Lupus Erythematosus (SLE)</condition>
    <arm_group>
      <arm_group_label>BRL-301</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Allogeneic CD19-targeted Chimeric AntigenReceptor (CAR) T Cells</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>BRL-301</intervention_name>
      <description>Single dose of Allogeneic Anti-CD19 CAR T cells will be infused</description>
      <arm_group_label>BRL-301</arm_group_label>
      <other_name>Allogeneic Anti-CD19 CAR T cells</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age range from 18 to 65 years old (including threshold), regardless of gender;&#xD;
  &#xD;
            2. Subjects diagnosed with SLE according to the 2019 EULAR/ACR SLE classification&#xD;
               criteria; ANA ≥ 1:80, or positive for anti dsDNA and/or anti Sm antibodies;&#xD;
  &#xD;
            3. Routine treatment is ineffective or the disease relapses after remission. Definition&#xD;
               of routine treatment: use more than two drugs, including glucocorticoid (more than&#xD;
               1mg/kg/d) and Cyclophosphamide, and any one or more of the following immunomodulatory&#xD;
               drugs for more than 6 months: Antimalarial medication, Azathioprine, mycophenolate&#xD;
               mofetil, methotrexate, leflunomide, Tacrolimus, Ciclosporin, and biological agents,&#xD;
               including rituximab, belizumab, or telitacicept&#xD;
  &#xD;
            4. At least one BILAG2004 Class A or two Class B score, or both;&#xD;
  &#xD;
            5. SELENA-SLEDAI score ≥ 8 points;&#xD;
  &#xD;
            6. The positive expression and expression rate of CD19 on peripheral blood B cells&#xD;
               determined by flow cytometry;&#xD;
  &#xD;
            7. The functions of important organs meet the following requirements:&#xD;
  &#xD;
               Bone marrow function needs to meet:&#xD;
  &#xD;
                 1. White blood cell count ≥ 3 × 109/L;&#xD;
  &#xD;
                 2. Neutrophil count ≥ 1 × 109/L (no Colony-stimulating factor treatment within 2&#xD;
                    weeks before examination);&#xD;
  &#xD;
                 3. Platelets ≥ 50 × 109/L;d. Hemoglobin ≥ 80g/L&#xD;
  &#xD;
               Liver function:&#xD;
  &#xD;
                 1. Alanine Aminotransferase (ALT) ≤ 3 × ULN;&#xD;
  &#xD;
                 2. Asparagus cochinchinensis transase (AST) ≤ 3 × ULN;&#xD;
  &#xD;
                 3. Total Bilirubin (TBIL) in serum ≤ 1.5 × ULN (excluding Gilbert syndrome, total&#xD;
                    bilirubin ≤ 3.0 × ULN); Renal function: Creatinine Clearance Rate (CrCl) ≥ 60&#xD;
                    ml/minute (Cockcroft/Fault formula) ;&#xD;
  &#xD;
               Coagulation function:&#xD;
  &#xD;
                 1. International Normalized Ratio (INR) ≤ 1.5 × ULN,&#xD;
  &#xD;
                 2. Prothrombin time (PT) ≤ 1.5 × ULN.&#xD;
  &#xD;
               Cardiac function: good hemodynamic stability, left ventricular Ejection fraction&#xD;
               (LVEF) ≥ 55%;&#xD;
  &#xD;
            8. Female patients of childbearing potential and male patients whose female sexual&#xD;
               partners are of childbearing age should adopt medically recognized contraceptive&#xD;
               measures or abstain from sex within at least 6 months after infusion of BRL-301;&#xD;
               female patients of childbearing age should have a negative serum HCG test result&#xD;
               within 7 days before study enrollment and be not breastfeeding;&#xD;
  &#xD;
            9. Willing to participate in this clinical study, sign an ICF, and complete follow-ups,&#xD;
               with good compliance.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Have a serious history of Drug allergy or allergic constitution;&#xD;
  &#xD;
            2. Fungi, bacteria, viruses, or other infections that are uncontrollable or require&#xD;
               intravenous medication treatment exist or are suspected;&#xD;
  &#xD;
            3. Central nervous system disease caused by SLE or not (including epilepsy, psychosis,&#xD;
               organic encephalopathy syndrome, cerebrovascular accident, encephalitis, central&#xD;
               nervous system Vasculitis);&#xD;
  &#xD;
            4. Individuals with relatively serious heart diseases, such as angina pectoris,&#xD;
               myocardial infarction, heart failure, and arrhythmia;&#xD;
  &#xD;
            5. Subjects with congenital immunoglobulin deficiency;&#xD;
  &#xD;
            6. Other malignant tumors (excluding non Melanoma skin cancer, cervical cancer in situ,&#xD;
               bladder cancer cancer and breast cancer that have survived for more than 5 years&#xD;
               without disease);&#xD;
  &#xD;
            7. Subjects with end-stage renal failure;&#xD;
  &#xD;
            8. Have received any of the following SLE treatments:&#xD;
  &#xD;
                 1. Corticosteroid (defined as prednisone or equivalent&gt;20 mg/day) of therapeutic&#xD;
                    dose were used before enrollment or within 72 hours before BRL-301 infusion.&#xD;
  &#xD;
                 2. Use any other clinical study drugs for SLE within 4 weeks prior to enrollment.&#xD;
                    However, if the research treatment period is ineffective or the disease&#xD;
                    progresses, and at least 3 half-lives have passed before enrollment, enrollment&#xD;
                    is allowed.&#xD;
  &#xD;
                 3. Had received anti CD20 monoclonal antibody (such as Rituximab) within 4 weeks&#xD;
                    before screening, tetaximab within 6 weeks, or belizumab within 12 weeks.&#xD;
  &#xD;
                 4. Previous CAR-T cell or other genetically modified T Cell therapy.&#xD;
  &#xD;
            9. Subjects with positive hepatitis B B surface antigen (HBsAg) or hepatitis B core&#xD;
               antibody (HBcAb) and HBV DNA titer in peripheral blood higher than the upper limit of&#xD;
               detection; Patients with positive hepatitis C virus (HCV) antibodies and positive&#xD;
               peripheral blood HCV RNA; People who are positive for human immunodeficiency virus&#xD;
               (HIV) antibodies; Those who have tested positive for syphilis;&#xD;
  &#xD;
           10. Having mental illness and severe cognitive impairment;&#xD;
  &#xD;
           11. Those who have participated in other clinical trials within the first 3 months of&#xD;
               enrollment;&#xD;
  &#xD;
           12. Pregnant or intending to conceive women;&#xD;
  &#xD;
           13. Patients who are unsuitable for being included into this study as deemed by the&#xD;
               investigator due to other reasons.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Hongyan Tong, Doctor</last_name>
      <phone>8613958122357</phone>
      <email>hongyantong@aliyun.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 4, 2023</study_first_submitted>
    <study_first_submitted_qc>August 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 13, 2023</last_update_submitted>
    <last_update_submitted_qc>August 13, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 15, 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>Lupus Erythematosus, Systemic</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/NCT05988216
  org study id: 2022-BRL-301A-SLE-IIT
  nct id: NCT05988216
  lead sponsor: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  This is an investigator initiated trial to assess the efficacy and safety of BRL-301 in the
        refractory systemic lupus erythematosus.
  The study had the following sequential phases: Screening, Pre-Treatment (Cell Product
        Preparation & Lymphodepleting Chemotherapy), Treatment and Follow-up.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: The safety of BRL-301 in refractory systemic lupus erythematosus
  time frame: 12 months
  description: Incidence and severity of AEs and SAEs, including changes in laboratory values, ECG and vital signs as assessed by CTCAE v5.0.
  measure: The efficiency of BRL-301 in refractory systemic lupus erythematosus
  time frame: 3 months
  description: Number of patients with SRI-4 response: including SELENA-SLEDAI ≥4-Point improvement, BILAG 2004 with No new A domain score AND no more than 1 new B domain scores, PGA with No worsening (<0.3-point increase)
  measure: Cellular kinetics
  time frame: 12 months
  description: CAR transgene levels by quantitative polymerase chain reaction (qPCR) in peripheral blood
  arm group label: BRL-301
  arm group type: Experimental
  description: Allogeneic CD19-targeted Chimeric AntigenReceptor (CAR) T Cells
  intervention type: Biological
  intervention name: BRL-301
  description: Single dose of Allogeneic Anti-CD19 CAR T cells will be infused
  arm group label: BRL-301
  other name: Allogeneic Anti-CD19 CAR T cells
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Hongyan Tong, Doctor
  phone: 8613958122357
  email: hongyantong@aliyun.com
  responsible party type: Sponsor
  mesh term: Lupus Erythematosus, Systemic
  sharing ipd: No