Clinical trial NCT06280378: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Transfusion-dependent Beta-Thalassemia
Keywords: gene therapy
lentiviral vector
KL003 cell injection
transfusion-dependent β-thalassemia
Lead sponsor: Kanglin Biotechnology (Hangzhou) Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-02-28
Enrollment: 41
Sex: ALL
Minimum age (years): 3
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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:

  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;

Primary outcomes:
measure: KL003 engraftment
timeFrame: From time of KL003 infusion through Month 2
measure: Engraftment time of neutrophil and platelet
timeFrame: From time of KL003 infusion through Month 24
measure: Overall Survival
timeFrame: From time of KL003 infusion through Month 24
measure: The number, frequency and severity of adverse events (AE) within 1 year after infusion of KL003 drug products
timeFrame: From time of KL003 infusion through Month 24
measure: Clonal dominance or secondary tumors caused by lentiviral vector insertional-mutation
timeFrame: From time of KL003 infusion through Month 24
measure: Numbers of Participants With Vector-Derived Replication-Competent Lentivirus (RCL)
timeFrame: From time of KL003 infusion through Month 24
Secondary outcomes:
measure: The proportion of participants achieved Transfusion Independence (TI)for at least 6 months
timeFrame: From time of KL003 infusion through Month 24
measure: The proportion of participants achieved TI 12
timeFrame: From time of KL003 infusion through Month 24
measure: The start time of Transfusion Independence (TI) after KL003 infusion
timeFrame: From time of KL003 infusion through Month 24
measure: Total Hb and the vector-derived HbA^T87Q
timeFrame: From time of KL003 infusion through Month 24
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
state: Tianjin
Study officials:
affiliation: R&D Kanglin Biotech
name: Haoquan Wu, PhD
role: STUDY_DIRECTOR
References: