A Phase I/II Clinical Study of the KL003 Cell Injection in β-Thalassemia Major Participants

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Transfusion-dependent Beta-Thalassemia
• Intervention / Treatment: Drug: KL003 Cell Injection Drug Product

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 Type: Interventional
• Enrollment (Estimated): 41
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: jingfeng Yan; Phone Number: +86 18852138866; Email: yanjingfeng@kanglinbio.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Ruijin Hospital, Shanghai Jiaotong University School of Medicine
      • Contact: Wei Tang, PhD; Phone Number: +86 13472889588
      • Principal Investigator: Saijuan Chen, PhD
  • Tianjin
    • Tianjin, Tianjin, China
      • Institute of Hematology & Blood Diseases Hospital
      • Contact: Zhen Gao, Master; Phone Number: +86 15522360862; Email: Gaozhen@ihcams.ac.cn
      • Principal Investigator: Jun Shi, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KL003 Cell Injection Drug Product; Transplant of auto-HSC transduced with lentiviral vector encoding βA-T87Q-globin gene	Drug: KL003 Cell Injection Drug Product; Administered by intravenous infusion after myeloablative conditioning with busulfan.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of participants achieved Transfusion Independence (TI)for at least 6 months	TI 6 is defined as Hb ≥ 90.0 g/L after reinfusion and without disease-related routine blood transfusion for 6 months	From time of KL003 infusion through Month 24
The proportion of participants achieved TI 12	TI 12 is defined as Hb ≥ 90.0 g/L after reinfusion and without disease-related routine blood transfusion for 12 months	From time of KL003 infusion through Month 24
The start time of Transfusion Independence (TI) after KL003 infusion	The TI start time is defined as the first day of treated participants with transfusion-dependent β-thalassemia (TDT) who achieved transfusion independence.	From time of KL003 infusion through Month 24
Total Hb and the vector-derived HbA^T87Q	The total Hb is measured by routine blood test, Therapeutic globin expression was measured by HbA^T87Q in peripheral blood.	From time of KL003 infusion through Month 24

Collaborators and Investigators

• Sponsor: Kanglin Biotechnology (Hangzhou) Co., Ltd.
• Investigators: Study Director: Haoquan Wu, PhD, R&D Kanglin Biotech

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: February 20, 2024
• First Submitted That Met QC Criteria: February 20, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: gene therapy; lentiviral vector; KL003; β-thalassemia
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Thalassemia; beta-Thalassemia
• Other Study ID Numbers: CP-KL003-003/01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No