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.

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.

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;