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A Phase I/II Clinical Study of the KL003 Cell Injection in β-Thalassemia Major Participants

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT06280378
Recruitment Status : Not yet recruiting
First Posted : February 28, 2024
Last Update Posted : February 28, 2024
Sponsor:
Information provided by (Responsible Party):
Kanglin Biotechnology (Hangzhou) Co., Ltd.

Brief Summary:
This is a non-randomized, open label, single-dose study in up to 41 participants with β-thalassemia major. The goal of this clinical trial is to evaluate the safety and efficacy of KL003 cell injection in subjects with β-thalassemia major.

Condition or disease Intervention/treatment Phase
Transfusion-dependent Beta-Thalassemia Drug: KL003 Cell Injection Drug Product Phase 1 Phase 2

Detailed Description:
This is a single-arm, multi-site, single-dose, Phase 1/2 study to assess KL003 Cell Injection in up to 41 participants with transfusion-dependent β-thalassemia (TDT) who are ≥3 and ≤35 years of age. KL003 Cell Injection is autologous CD34+ stem cells transduced Ex Vivo with a lentiviral Vector encoding βA-T87Q-Globin.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 41 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Clinical Study Evaluating the Safety and Efficacy of KL003 Cell Injection in Transfusion-dependent β-thalassemia
Estimated Study Start Date : February 2024
Estimated Primary Completion Date : May 2025
Estimated Study Completion Date : May 2027


Arm Intervention/treatment
Experimental: KL003 Cell Injection Drug Product
Transplant of auto-HSC transduced with lentiviral vector encoding βA-T87Q-globin gene
Drug: KL003 Cell Injection Drug Product
Administered by intravenous infusion after myeloablative conditioning with busulfan.




Primary Outcome Measures :
  1. KL003 engraftment [ Time Frame: From time of KL003 infusion through Month 2 ]
    Proportion of participants with successful engraftment within 42 days after KL003 infusion.

  2. Engraftment time of neutrophil and platelet [ Time Frame: From time of KL003 infusion through Month 24 ]
    Neutrophil engraftment was defined as the first day when neutrophils ≥ 0.5×10^9/L for 3 consecutive days; Platelet engraftment was defined as the first the first day of platelet count ≥ 20.0×10^9/L for 7 consecutive days with no platelet transfusions.

  3. Overall Survival [ Time Frame: From time of KL003 infusion through Month 24 ]
    Overall survival was defined as time from date of KL003 infusion to date of death.

  4. The number, frequency and severity of adverse events (AE) within 1 year after infusion of KL003 drug products [ Time Frame: From time of KL003 infusion through Month 24 ]
    Frequency and severity of AEs & SAEs identified according to NCI CTCAE 5.0

  5. Clonal dominance or secondary tumors caused by lentiviral vector insertional-mutation [ Time Frame: From time of KL003 infusion through Month 24 ]
    Clonal dominance was defined as an ISA result greater than 90% of the total insertion sites (IS) at any time

  6. Numbers of Participants With Vector-Derived Replication-Competent Lentivirus (RCL) [ Time Frame: From time of KL003 infusion through Month 24 ]
    Peripheral blood samples were analyzed for detection of RCL


Secondary Outcome Measures :
  1. The proportion of participants achieved Transfusion Independence (TI)for at least 6 months [ Time Frame: From time of KL003 infusion through Month 24 ]
    TI 6 is defined as Hb ≥ 90.0 g/L after reinfusion and without disease-related routine blood transfusion for 6 months

  2. The proportion of participants achieved TI 12 [ Time Frame: From time of KL003 infusion through Month 24 ]
    TI 12 is defined as Hb ≥ 90.0 g/L after reinfusion and without disease-related routine blood transfusion for 12 months

  3. The start time of Transfusion Independence (TI) after KL003 infusion [ Time Frame: From time of KL003 infusion through Month 24 ]
    The TI start time is defined as the first day of treated participants with transfusion-dependent β-thalassemia (TDT) who achieved transfusion independence.

  4. Total Hb and the vector-derived HbA^T87Q [ Time Frame: From time of KL003 infusion through Month 24 ]
    The total Hb is measured by routine blood test, Therapeutic globin expression was measured by HbA^T87Q in peripheral blood.



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Ages Eligible for Study:   3 Years to 35 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female age between 3-35 years;
  • Diagnosis of transfusion-dependent β-thalassemia and a history of at least 100 mL/kg/year of pRBCs or ≥8 transfusions of pRBCs per year for the prior 2 years;
  • Karnofsky performance status ≥70 for participants≥16 years of age; Lansky performance status of ≥70 for participants<16 years of age;
  • Eligible to undergo auto-HSCT;
  • Willing and able to follow the research procedures and conditions, with good compliance;
  • Willing to receive at least the 2 years follow-up;
  • Participant and/or legal guardians voluntarily participated in this clinical trial and signed the informed consent form.

Exclusion Criteria:

  • Diagnosis of composite α thalassemia;
  • Prior receipt of gene therapy or allo-HSCT;
  • Meet the criteria for allo-HSCT and with an identified willing donor with full HLA match;
  • Participants with severe iron overload at the time of screening;
  • Presence of unusual antibody of red blood cell antigens or tested positive for platelet antibody;
  • Known allergy to clinical trial drug (plerixafor or G-CSF or busulfan) or ingredient(DMSO etc.);
  • Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the clinical investigator;
  • Subjects positive with the following etiological tests: human immunodeficiency virus(HIV-1-2),human cytomegalovirus (HCMV-DNA),EB virus(EBV-DNA),HBV (HBsAg/HBV-DNA positive),HCV antibody (HCV-Ab), Human T-lymphotropic virus antibody (HTLV-Ab), Treponema pallidum antibody (TP-Ab);
  • Uncorrectable coagulation dysfunction or history of severe bleeding disorder;
  • History of major organ damage including:

    1. Liver function test suggest AST or ALT levels >3× upper limit of normal(ULN);
    2. Total serum bilirubin value>2.5×ULN;if combined with Gilbert syndrome, total bilirubin>3×ULN and direct bilirubin value>2.5×ULN;
    3. Left ventricular ejection fraction <45%;
    4. Baseline calculated eGFR<60mL/min/1.73m2;
    5. Pulmonary function:FEV1/FVC<60% and/or diffusion capacity of carbon monoxide (DLco) <60% of prediction;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06280378


Contacts
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Contact: jingfeng Yan +86 18852138866 yanjingfeng@kanglinbio.com

Locations
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China, Shanghai
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai, China
Contact: Wei Tang, PhD    +86 13472889588      
Principal Investigator: Saijuan Chen, PhD         
China, Tianjin
Institute of Hematology & Blood Diseases Hospital
Tianjin, Tianjin, China
Contact: Zhen Gao, Master    +86 15522360862    Gaozhen@ihcams.ac.cn   
Principal Investigator: Jun Shi, PhD         
Sponsors and Collaborators
Kanglin Biotechnology (Hangzhou) Co., Ltd.
Investigators
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Study Director: Haoquan Wu, PhD R&D Kanglin Biotech
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Responsible Party: Kanglin Biotechnology (Hangzhou) Co., Ltd.
ClinicalTrials.gov Identifier: NCT06280378    
Other Study ID Numbers: CP-KL003-003/01
First Posted: February 28, 2024    Key Record Dates
Last Update Posted: February 28, 2024
Last Verified: February 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kanglin Biotechnology (Hangzhou) Co., Ltd.:
gene therapy; lentiviral vector; KL003; β-thalassemia
Additional relevant MeSH terms:
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Thalassemia
beta-Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn