Β-Thalassemia Treatment with KL003 Cell Injection

NCT06280378 | Recruiting Phase 1

• 1 other identifier: CP-KL003-003/01
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

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.

Conditions

Transfusion-dependent Beta-Thalassemia

Keywords

gene therapy; lentiviral vector; KL003 cell injection; transfusion-dependent β-thalassemia

Outcome Measures

Primary Outcomes (6)

• KL003 engraftment

  Proportion of participants with successful engraftment within 42 days after KL003 infusion.

  From time of KL003 infusion through Month 2

• Engraftment time of neutrophil and platelet

  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.

  From time of KL003 infusion through Month 24

• Overall Survival

  Overall survival was defined as time from date of KL003 infusion to date of death.

  From time of KL003 infusion through Month 24

• The number, frequency and severity of adverse events (AE) within 1 year after infusion of KL003 drug products

  Frequency and severity of AEs \& SAEs identified according to NCI CTCAE 5.0

  From time of KL003 infusion through Month 24

• Clonal dominance or secondary tumors caused by lentiviral vector insertional-mutation

  Clonal dominance was defined as an ISA result greater than 90% of the total insertion sites (IS) at any time

  From time of KL003 infusion through Month 24

• Numbers of Participants With Vector-Derived Replication-Competent Lentivirus (RCL)

  Peripheral blood samples were analyzed for detection of RCL

  From time of KL003 infusion through Month 24

Secondary Outcomes (4)

• The proportion of participants achieved Transfusion Independence (TI)for at least 6 months

  From time of KL003 infusion through Month 24

• The proportion of participants achieved TI 12

  From time of KL003 infusion through Month 24

• The start time of Transfusion Independence (TI) after KL003 infusion

  From time of KL003 infusion through Month 24

• Total Hb and the vector-derived HbA^T87Q

  From time of KL003 infusion through Month 24

Study Arms (1)

KL003 Cell Injection Drug Product

EXPERIMENTAL

Transplant of auto-HSC transduced with lentiviral vector encoding βA-T87Q-globin gene

Drug: KL003 Cell Injection Drug Product

Interventions

KL003 Cell Injection Drug Product DRUG

Administered by intravenous infusion after myeloablative conditioning with busulfan.

KL003 Cell Injection Drug Product

Eligibility Criteria

• Age: 3 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Kanglin Biotechnology (Hangzhou) Co., Ltd.: lead

Study Sites (2)

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, China

RECRUITING

Institute of Hematology & Blood Diseases Hospital

Tianjin, Tianjin Municipality, China

RECRUITING

Study Officials

• Haoquan Wu, PhD

  R&D Kanglin Biotech

  STUDY DIRECTOR

Central Study Contacts

jingfeng Yan

CONTACT

+86 18852138866; yanjingfeng@kanglinbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2024
• First Posted: February 28, 2024
• Study Start: April 5, 2024
• Primary Completion: October 1, 2025
• Study Completion (Estimated): May 1, 2027
• Last Updated: March 10, 2025

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)