Β-Thalassemia Treatment with KL003 Cell Injection

Phase 1

Recruiting

• Conditions: Transfusion-dependent Beta-Thalassemia
• Interventions: Drug: KL003 Cell Injection Drug Product

• Registration Number: NCT06280378
• Lead Sponsor: 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.

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.

Study Timeline

• Study First Submitted: 2024-02-20
• Study First Submitted QC: 2024-02-20
• Study First Posted: 2024-02-28
• Status Verified: 2024-04
• Study Start: 2024-04-05
• Last Update Submitted: 2025-03-06
• Last Update Posted: 2025-03-10
• Primary Completion: 2025-10
• Study Completion: 2027-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 41

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;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
KL003 Cell Injection Drug Product	KL003 Cell Injection Drug Product	Transplant of auto-HSC transduced with lentiviral vector encoding βA-T87Q-globin gene

Primary Outcome Measures

Name	Time	Method
KL003 engraftment	From time of KL003 infusion through Month 2	Proportion of participants with successful engraftment within 42 days after KL003 infusion.
The number, frequency and severity of adverse events (AE) within 1 year after infusion of KL003 drug products	From time of KL003 infusion through Month 24	Frequency and severity of AEs \& SAEs identified according to NCI CTCAE 5.0
Clonal dominance or secondary tumors caused by lentiviral vector insertional-mutation	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
Numbers of Participants With Vector-Derived Replication-Competent Lentivirus (RCL)	From time of KL003 infusion through Month 24	Peripheral blood samples were analyzed for detection of RCL
Engraftment time of neutrophil and platelet	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.
Overall Survival	From time of KL003 infusion through Month 24	Overall survival was defined as time from date of KL003 infusion to date of death.

Secondary Outcome Measures

Name	Time	Method
The proportion of participants achieved Transfusion Independence (TI)for at least 6 months	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
The proportion of participants achieved TI 12	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
The start time of Transfusion Independence (TI) after KL003 infusion	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.
Total Hb and the vector-derived HbA^T87Q	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.

Trial Locations

Locations (2)

Ruijin Hospital, Shanghai Jiaotong University School of Medicine; 🇨🇳 Shanghai, Shanghai, China

Institute of Hematology & Blood Diseases Hospital; 🇨🇳 Tianjin, Tianjin, China