Treatment for Beta-Thalassemia using KL003 Cell Injection

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

This study is testing a new gene therapy using KL003 cell injections to see if it can help young people with severe beta-thalassemia reduce their need for blood transfusions.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 41 (estimated)
• Ages: 3 Years to 35 Years
• Sex: All
• Sponsor: Kanglin Biotechnology (Hangzhou) Co., Ltd. (Industry-sponsored)
• Locations: 2 sites (Shanghai, Shanghai Municipality and 1 other locations)
• Trial ID: NCT06280378 on ClinicalTrials.gov

What this trial studies

This clinical trial is a non-randomized, open-label, single-dose study aimed at evaluating the safety and efficacy of KL003 cell injection in participants with transfusion-dependent β-thalassemia major. The study will involve up to 41 participants aged between 3 and 35 years, who will receive autologous CD34+ stem cells that have been modified using a lentiviral vector to produce βA-T87Q-Globin. The trial will assess the outcomes of this innovative gene therapy approach over a follow-up period of at least two years.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals aged 3 to 35 years with a diagnosis of transfusion-dependent β-thalassemia who have a history of frequent blood transfusions.

Not a fit: Patients with severe iron overload, prior gene therapy, or those who are eligible for allo-HSCT with a matched donor may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce or eliminate the need for blood transfusions in patients with β-thalassemia.

How similar studies have performed: Other studies using gene therapy approaches for β-thalassemia have shown promising results, indicating potential for success in this novel treatment.

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;

Where this trial is running

Shanghai, Shanghai Municipality and 1 other locations

• 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 contacts

• Study coordinator: jingfeng Yan

Conditions Transfusion-dependent Beta-Thalassemia; gene therapy; lentiviral vector; KL003 cell injection; transfusion-dependent β-thalassemia