Evaluation the Safety and Efficacy of KL003 Cell Injection in the Treatment of Transfusion-dependent β-thalassemia.

This is a non-randomized, open-label, single-dose study. The aim of this study is to evaluate the safety and efficacy of the treatment with lentiviral vector encoding βA-T87Q-globin gene transduced autologous hematopoietic stem cells in subjects with transfusion-dependent β-thalassemia.

Study Overview

• Status: Active, not recruiting
• Conditions: Transfusion-dependent Beta-Thalassemia
• Intervention / Treatment: Genetic: KL003 cell injection Drug Product

Detailed Description

Subject participation for this study will be 24 months. Subjects who enroll in this study will be asked to participate in a subsequent 13-year follow-up for gene therapy products.

• Study Type: Interventional
• Enrollment (Estimated): 3
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China
      • Regenerative Medicine Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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
• Documented baseline, or pretransfusion, Hb level≤7 g/dL
• Karnofsky performance status ≥70 for subjects≥16 years of age; Lansky performance status of ≥70 for subjects<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 and maintain detailed medical records, including transfusion history
• Subject and/or legal guardians voluntarily participated in this clinical trial and signed the informed consent form, and can complete all follow-up in accordance with the protocol requirements

Exclusion Criteria:

• 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), Treponema pallidum antibody (TP-Ab)
• Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the clinical investigator
• Contraindication to bone marrow collection
• Any prior or current malignancy or myeloproliferative or significant immunodeficiency disorder
• A white blood cell (WBC) count <3×10^9/L, and/or platelet count <100×10^9/L not related to hypersplenism
• Diagnosis of composite α thalassemia
• Participants with severe iron overload at the time of screening: severe iron overload of the liver showed by MRI, serum ferritin ≥ 5000 ng/mL, or moderate to severe iron overload of the heart
• Presence of unusual antibody of red blood cell antigens or tested positive for platelet antibody
• Meet the criteria for allo-HSCT and with an identified willing donor with a full HLA match
• Prior receipt of gene therapy or allo-HSCT
• Immediate family member (i.e. parent or siblings) with a known Familial Cancer Syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary non-polyposis colorectal cancer syndrome and familial adenomatous polyposis)
• Diagnosis of a significant psychiatric disorder of the subject that could seriously impede the ability to participate in the study

• 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. History of bridging fibrosis, cirrhosis;
  4. Left ventricular ejection fraction <45%;
  5. New York Heart Association (NYHA) class III or IV congestive heart failure;
  6. Severe arrhythmia requiring medical treatment;
  7. Uncontrolled hypertension or unstable angina pectoris;
  8. Myocardial infarction or bypass or stent surgery within 12 months before drug administration;
  9. Valvular disease with clinical significance;
  10. Baseline calculated eGFR<60mL/min/1.73m2;
  11. Pulmonary function: FEV1/FVC<60% and/or diffusion capacity of carbon monoxide (DLco) <60% of prediction;
  12. Evidence of clinically significant pulmonary hypertension requiring medical intervention.
• Uncorrectable coagulation dysfunction or history of severe bleeding disorder
• Any other condition that would render the subject ineligible for HSCT, as determined by the attending transplant physician
• Known allergy to clinical trial drug (plerixafor or G-CSF or busulfan) or ingredient(DMSO etc.)
• Participation in another clinical study with an investigational drug within 30 days of Screening or participating in another clinical study with an investigational drug
• Inoculated live vaccine within 6 weeks prior to screening
• Pregnancy or breastfeeding women; Subjects or their sexual partners were unable to take medically recognized effective contraceptive measures during the 27-month study period
• The subjects or their parents would not comply with the study procedures outlined in the protocol
• Receipt of hydroxyurea therapy within 3 months before HSCT harvest
• Patients considered to be ineligible for the study by the investigator for reasons other than the above

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KL003 cell injection Drug Product; Each recruited subject will accept KL003 Transplantation.	Genetic: KL003 cell injection Drug Product; Transplant of auto-HSC transduced with lentiviral vector encoding βA-T87Q-globin gene.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with successful lentiviral vector transduced CD34+ stem cell engraftment	Successful engraftment was defined as neutrophil count [ANC] ≥0.5×10^9/L for 3 consecutive days	Up to 42 days post transplant
Engraftment time of neutrophil	The first day when neutrophils ≥ 0.5×10^9/L for 3 consecutive days	Up to 42 days post transplant
Engraftment time of platelet	The first day of platelet count ≥ 20.0×10^9/L for 7 consecutive days after platelet transfusion independence	Up to 42 days post transplant
Transplant-related mortality within 100 days and within 1 year after reinfusion of KL003 drug product		Up to 1 year post transplant
The number, frequency and severity of adverse events (AE) within 1 year after reinfusion of KL003 drug products	Frequency and severity of AEs & SAEs identified according to NCI CTCAE 5.0	Up to 24 months post transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of participants who meet the definition of transfusion independence (TI) for at least 6 months	TI is defined as Hb ≥ 90.0 g/L after reinfusion and without disease-related routine blood transfusion for 6 months	Up to 24 months post transplant
The duration of transfusion independence		Up to 24 months post transplant
Changes in the frequency and volume of blood transfusion		Up to 24 months post transplant

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Collaborators: R&D Kanglin Biotech

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2023
• Primary Completion (Estimated): August 20, 2025
• Study Completion (Estimated): October 24, 2025

Study Registration Dates

• First Submitted: May 8, 2023
• First Submitted That Met QC Criteria: May 8, 2023
• First Posted (Actual): May 16, 2023

Study Record Updates

• Last Update Posted (Actual): August 5, 2025
• Last Update Submitted That Met QC Criteria: July 31, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Beta-Thalassaemia; Hematopoietic Stem-Cell Transplantation
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Thalassemia; beta-Thalassemia
• Other Study ID Numbers: IIT2023021

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No