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/NCT06010472</url>
    </required_header>
    <id_info>
      <org_study_id>CHEC2023-174</org_study_id>
      <nct_id>NCT06010472</nct_id>
    </id_info>
    <brief_title>An Exploratory Clinical Study of Anti-CD19 CAR NK Cells in the Treatment of Systemic Lupus Erythematosus</brief_title>
    <official_title>An Exploratory Clinical Study of the Safety and Efficacy of Anti-CD19 Chimeric Antigen Receptor (CAR) Nature Killer Cells (KN5501) in the Treatment of Moderate to Severe Refractory Systemic Lupus Erythematosus (SLE)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Changhai Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Nanjing Enricnk Biotech Co., Ltd</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Changhai Hospital</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>
        A single arm, open-label pilot study is designed to determine the safety and effectiveness of&#xD;
        anti-cluster of differentiation antigen 19 (CD19) chimeric antigen receptor (CAR) natural&#xD;
        killer (NK) cells (KN5501) in patients with moderate to severe refractory systemic lupus&#xD;
        erythematosus (SLE). 9-12 patients are planned to be enrolled in the dose-escalation trial&#xD;
        (3×10^8 cells, 6×10^8 cells, 1.2×10^9 cells). The primary objective of the study was to&#xD;
        evaluate the safety of allogeneic anti-CD19 CAR-NK cells (KN5501) for the treatment of&#xD;
        patients with moderate to severe refractory active SLE. The secondary objective is to&#xD;
        evaluate the efficacy of anti-CD19 CAR NK cells (KN5501) in patients with moderate to severe&#xD;
        refractory SLE, including British Isles Lupus Assessment Group 2004 (BILAG-2004) index,&#xD;
        Systemic Lupus Erythematosus Responder Index (SRI)-4 response rate, Lupus Low Disease&#xD;
        Activity State (LLDAS) rate, and Definitions Of Remission In SLE (DORIS) remission rate.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 24, 2023</start_date>
    <completion_date type="Anticipated">August 25, 2025</completion_date>
    <primary_completion_date type="Anticipated">August 25, 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>Incidence of Dose Limiting Toxicity (DLTs)</measure>
      <time_frame>within 4 weeks after infusion; 12, 24, 36 and 52 weeks after infusion</time_frame>
      <description>To characterize the safety of anti-CD19 CAR NK Cells for moderate to severe refractory SLE</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Incidence of Treatment Emergent Adverse Events (TEAEs)</measure>
      <time_frame>within 4 weeks after infusion; 12, 24, 36 and 52 weeks after infusion</time_frame>
      <description>To characterize the safety of anti-CD19 CAR NK Cells for moderate to severe refractory SLE</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>SRI-4 response rate of subjects</measure>
      <time_frame>12, 24,36, and 52 weeks after infusion</time_frame>
      <description>To characterize the efficacy of anti-CD19 CAR NK Cells for moderate to severe refractory SLE</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>LLDAS rate of subjects</measure>
      <time_frame>12, 24,36, and 52 weeks after infusion</time_frame>
      <description>To characterize the efficacy of anti-CD19 CAR NK Cells for moderate to severe refractory SLE</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>DORIS remission rate of subjects</measure>
      <time_frame>12, 24,36, and 52 weeks after infusion</time_frame>
      <description>To characterize the efficacy of anti-CD19 CAR NK Cells for moderate to severe refractory SLE</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>anti-CD19 CAR NK cells</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>To evaluate the safety and effectiveness of anti-CD19 CAR NK cells (KN5501) in patients with moderate to severe refractory SLE. All subjects will receive fludarabine/cyclophosphamide lymphodepletion followed by anti-CD19 CAR NK cells infusion on Day 0, 7, and 14.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>anti-CD19 CAR NK cells (KN5501)</intervention_name>
      <description>Patients will receive Fludarabine (25 mg/m2 per day) and Cyclophosphamide (300mg/m2 per day) on day -5, -4, and -3. Doses of 3×10^8, 6×10^8, 1.2×10^9 anti-CD19 CAR NK cells (KN5501) will infused in each group using the &quot;3 + 3&quot; dose-escalation strategy.</description>
      <arm_group_label>anti-CD19 CAR NK cells</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age: ≥ 18 years old and ≤ 65 years old, male or female, subjects voluntarily&#xD;
               participate in this clinical study and sign the Informed Consent Form (ICF)&#xD;
  &#xD;
            2. Previous diagnosis of systemic lupus erythematosus (SLE) (according to the 1997&#xD;
               American Rheumatology Association criteria)&#xD;
  &#xD;
            3. Females of childbearing potential must use effective contraception during study&#xD;
               treatment and for 90 days after the last dose of study treatment. In addition,&#xD;
               subjects must not donate eggs during the study and for at least 90 days after the last&#xD;
               dose of study treatment&#xD;
  &#xD;
            4. Subjects with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) score ≥&#xD;
               8 points prior to screening&#xD;
  &#xD;
            5. Subject has ≥ 1 organ system with BILAG-2004 Class A mobility score or ≥ 2 organ&#xD;
               systems with BILAG-2004 Class B mobility score prior to screening&#xD;
  &#xD;
            6. Subjects meets one of the following:&#xD;
  &#xD;
                 1. Antinuclear antibody (ANA) ≥ 1:80, determined by immunofluorescence method;&#xD;
  &#xD;
                 2. Anti-dsDNA antibodies are higher than normal level;&#xD;
  &#xD;
                 3. Anti-Smith antibodies are higher than normal level&#xD;
  &#xD;
            7. Absolute number of neutrophils ≥ 1.0×109/L, hemoglobin ≥ 60g/L, platelets ≥ 50×109/L&#xD;
  &#xD;
            8. Left ventricular ejection fraction (LVEF) ≥ 50%&#xD;
  &#xD;
            9. Subjects have been treated with oral corticosteroids (OCS) in combination with an&#xD;
               immunosuppressive or biologic agent for at least 6 months prior to enrollment&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Subjects with known severe allergic reactions, hypersensitivity, contraindication to&#xD;
               any medications during the trial (cyclophosphamide, fludarabine, obinutuzumab), or&#xD;
               subjects with a history of severe allergic reactions&#xD;
  &#xD;
            2. Subjects with active infection receiving intravenous (IV) antibiotic treatment, or&#xD;
               received intravenous (IV) antibiotic treatment within one week prior to anti-CD19 CAR&#xD;
               NK Cells infusion&#xD;
  &#xD;
            3. Subjects with acquired and congenital immunodeficiency diseases&#xD;
  &#xD;
            4. Subjects with grade III or IV heart failure (NYHA classification)&#xD;
  &#xD;
            5. History of epilepsy or other central nervous system (CNS) diseases&#xD;
  &#xD;
            6. History of severe herpetic infection, such as herpetic encephalitis, ocular herpes, or&#xD;
               diffuse herpes&#xD;
  &#xD;
            7. History of other primary malignant tumors except:&#xD;
  &#xD;
                 1. Cured non-melanoma skin cancer by surgical excision, for example basal cell&#xD;
                    carcinoma (BCC) ;&#xD;
  &#xD;
                 2. Cured primary malignant tumors, such as cervical cancer, superficial bladder&#xD;
                    cancer, breast cancer&#xD;
  &#xD;
            8. Signs of herpes or varicella-zoster virus infection (especially chickenpox, shingles)&#xD;
               within 12 weeks prior to screening; History of any cardiac, endocrine, hematologic,&#xD;
               hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic,&#xD;
               psychiatric, and renal disease or other major medical condition that would prevent the&#xD;
               administration of anti-CD19 CAR NK Cells (KN5501), except for lupus (determined by the&#xD;
               investigator)&#xD;
  &#xD;
            9. Females who are pregnant, lactating, or planning a pregnancy within six months&#xD;
  &#xD;
           10. Any active skin disease that may interfere with the study assessment of SLE, including&#xD;
               but not limited to psoriasis, dermatomyositis, systemic sclerosis, non-LE cutaneous&#xD;
               lupus manifestations (eg, cutaneous vascular disease, periungual telangiectasia,&#xD;
               fingertip sclerosis, rheumatoid nodules, erythema multiforme, leg ulcers) or&#xD;
               drug-induced lupus&#xD;
  &#xD;
           11. Subjects who have received other clinical trial treatment within 3 months&#xD;
  &#xD;
           12. Subjects who have received B cell-targeted drug therapy within 1 month before&#xD;
               enrollment&#xD;
  &#xD;
           13. Any abnormal laboratory test results judged by the investigator to be clinically&#xD;
               significant and prevent the subject from participating in the study. Laboratory test&#xD;
               values that are out of range and not of clinical significance will not be considered&#xD;
               as exclusion criteria&#xD;
  &#xD;
           14. Any situation judged by the investigators that may increase the risk of the subjects&#xD;
               or interfere with the clinical trial outcome&#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_official>
      <last_name>Dongbao Zhao, Doctor</last_name>
      <role>Principal Investigator</role>
      <affiliation>ChanghaiHospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Dongbao Zhao, Doctor</last_name>
      <phone>+86-15921061314</phone>
      <email>dongbaozhao@163.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Changhai Hospital</name>
        <address>
          <city>Shanghai</city>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Dongbao Dongbao Zhao, Doctor</last_name>
        <phone>+86-15921061314</phone>
        <email>dongbaozhao@163.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 7, 2023</study_first_submitted>
    <study_first_submitted_qc>August 23, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 24, 2023</study_first_posted>
    <last_update_submitted>August 25, 2023</last_update_submitted>
    <last_update_submitted_qc>August 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 28, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Lupus Erythematosus, Systemic</keyword>
    <keyword>Autoimmune disorders</keyword>
    <keyword>Connective Tissue Diseases</keyword>
    <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/NCT06010472
  org study id: CHEC2023-174
  nct id: NCT06010472
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  A single arm, open-label pilot study is designed to determine the safety and effectiveness of
        anti-cluster of differentiation antigen 19 (CD19) chimeric antigen receptor (CAR) natural
        killer (NK) cells (KN5501) in patients with moderate to severe refractory systemic lupus
        erythematosus (SLE). 9-12 patients are planned to be enrolled in the dose-escalation trial
        (3×10^8 cells, 6×10^8 cells, 1.2×10^9 cells). The primary objective of the study was to
        evaluate the safety of allogeneic anti-CD19 CAR-NK cells (KN5501) for the treatment of
        patients with moderate to severe refractory active SLE. The secondary objective is to
        evaluate the efficacy of anti-CD19 CAR NK cells (KN5501) in patients with moderate to severe
        refractory SLE, including British Isles Lupus Assessment Group 2004 (BILAG-2004) index,
        Systemic Lupus Erythematosus Responder Index (SRI)-4 response rate, Lupus Low Disease
        Activity State (LLDAS) rate, and Definitions Of Remission In SLE (DORIS) remission rate.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence of Dose Limiting Toxicity (DLTs)
  time frame: within 4 weeks after infusion; 12, 24, 36 and 52 weeks after infusion
  description: To characterize the safety of anti-CD19 CAR NK Cells for moderate to severe refractory SLE
  measure: Incidence of Treatment Emergent Adverse Events (TEAEs)
  time frame: within 4 weeks after infusion; 12, 24, 36 and 52 weeks after infusion
  description: To characterize the safety of anti-CD19 CAR NK Cells for moderate to severe refractory SLE
  measure: SRI-4 response rate of subjects
  time frame: 12, 24,36, and 52 weeks after infusion
  description: To characterize the efficacy of anti-CD19 CAR NK Cells for moderate to severe refractory SLE
  measure: LLDAS rate of subjects
  time frame: 12, 24,36, and 52 weeks after infusion
  description: To characterize the efficacy of anti-CD19 CAR NK Cells for moderate to severe refractory SLE
  measure: DORIS remission rate of subjects
  time frame: 12, 24,36, and 52 weeks after infusion
  description: To characterize the efficacy of anti-CD19 CAR NK Cells for moderate to severe refractory SLE
  arm group label: anti-CD19 CAR NK cells
  arm group type: Experimental
  description: To evaluate the safety and effectiveness of anti-CD19 CAR NK cells (KN5501) in patients with moderate to severe refractory SLE. All subjects will receive fludarabine/cyclophosphamide lymphodepletion followed by anti-CD19 CAR NK cells infusion on Day 0, 7, and 14.
  intervention type: Drug
  intervention name: anti-CD19 CAR NK cells (KN5501)
  description: Patients will receive Fludarabine (25 mg/m2 per day) and Cyclophosphamide (300mg/m2 per day) on day -5, -4, and -3. Doses of 3×10^8, 6×10^8, 1.2×10^9 anti-CD19 CAR NK cells (KN5501) will infused in each group using the "3 + 3" dose-escalation strategy.
  arm group label: anti-CD19 CAR NK cells
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Dongbao Zhao, Doctor
  role: Principal Investigator
  affiliation: ChanghaiHospital
  last name: Dongbao Zhao, Doctor
  phone: +86-15921061314
  email: dongbaozhao@163.com
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Lupus Erythematosus, Systemic
  sharing ipd: No