Β-Thalassemia Treatment with KL003 Cell Injection

Official title

A Phase I/II Clinical Study Evaluating the Safety and Efficacy of KL003 Cell Injection in Transfusion-dependent Β-thalassemia

Overview

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.

Interventions

• Drug KL003 Cell Injection Drug Product
  Administered by intravenous infusion after myeloablative conditioning with busulfan.

Primary outcome measures

• KL003 engraftment [Time frame: From time of KL003 infusion through Month 2]
• Engraftment time of neutrophil and platelet [Time frame: From time of KL003 infusion through Month 24]
• Overall Survival [Time frame: 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 [Time frame: From time of KL003 infusion through Month 24]
• Clonal dominance or secondary tumors caused by lentiviral vector insertional-mutation [Time frame: From time of KL003 infusion through Month 24]
• Numbers of Participants With Vector-Derived Replication-Competent Lentivirus (RCL) [Time frame: From time of KL003 infusion through Month 24]

Secondary outcome measures (4)

• The proportion of participants achieved Transfusion Independence (TI)for at least 6 months [Time frame: From time of KL003 infusion through Month 24]
• The proportion of participants achieved TI 12 [Time frame: From time of KL003 infusion through Month 24]
• The start time of Transfusion Independence (TI) after KL003 infusion [Time frame: From time of KL003 infusion through Month 24]
• Total Hb and the vector-derived HbA^T87Q [Time frame: From time of KL003 infusion through Month 24]

Eligibility 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:

• 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;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

• Ruijin Hospital, Shanghai Jiaotong University School of Medicine — Shanghai
• Institute of Hematology & Blood Diseases Hospital — Tianjin

Identifiers

NCT: NCT06280378 · CP-KL003-003/01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗