Evaluation of the Safety and Efficacy of KL003 Gene Therapy in Patients With Transfusion-dependent β-thalassemia With No Conditioning Regimen

CP-KL003-004/01

This is a non-randomized, open-label, single-dose study. The aim of this study is to evaluate the safety and efficacy of the treatment with lentiviral vector encoding βA-T87Q-globin gene transduced autologous hematopoietic stem cells transfusion in subjects with β-thalassemia major.

2024-01-04

2025-12-31

2026-12-31

Recruiting

3

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 * Documented baseline, or pretransfusion, Hb level≤7 g/dL * Karnofsky performance status ≥70 for subjects≥16 years of age; Lansky performance status of ≥70 for subjects\<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 and maintain detailed medical records, including transfusion history * Subject and/or legal guardians voluntarily participated in this clinical trial and signed the informed consent form, and can complete all follow-ups in accordance with the protocol requirements Exclusion Criteria: * Presence of clear contraindications for hematopoietic stem cell collection * Diagnosis of composite α thalassemia * A white blood cell (WBC) count \<3×10\^9/L, and/or platelet count \<100×10\^9/L not related to hypersplenism * Subjects with severe iron overload at the time of screening: severe iron overload of the liver showed by MRI, serum ferritin ≥ 5000 ng/mL, or moderate to severe iron overload of the heart * Any prior or current malignancy or myeloproliferative or significant immunodeficiency disorder * Meet the criteria for allo-HSCT and with an identified willing donor with a full HLA match * Prior receipt of gene therapy or allo-HSCT * Subjects with any severe active fungal, bacterial, viral, tuberculosis or other infection, including active hepatitis B (defined as serum HBV-DNA ≥2000 IU/ml), active hepatitis C virus, HCV) infection, human immunodeficiency virus (HIV) antibody-positive or active syphilis patients, etc. * Immediate family member (i.e. parent or siblings) with a known Familial Cancer Syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary non-polyposis colorectal cancer syndrome and familial adenomatous polyposis) * Diagnosis of a significant psychiatric disorder of the subject that could seriously impede the ability to participate in the study * 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. History of bridging fibrosis, cirrhosis; 4. Left ventricular ejection fraction \<45%; 5. New York Heart Association (NYHA) class III or IV congestive heart failure; 6. Severe arrhythmia requiring medical treatment; 7. Uncontrolled hypertension or unstable angina pectoris; 8. Myocardial infarction or bypass or stent surgery within 12 months before drug administration; 9. Valvular disease with clinical significance; 10. Baseline calculated eGFR\<60mL/min/1.73m2; 11. Pulmonary function: FEV1/FVC\<60% and/or diffusion capacity of carbon monoxide (DLco) \<60% of prediction; 12. Evidence of clinically significant pulmonary hypertension requiring medical intervention. * Uncorrectable coagulation dysfunction or history of severe bleeding disorder * Any other condition that would render the subject ineligible for HSCT, as determined by the attending transplant physician * Known allergy to clinical trial drug (plerixafor or G-CSF or busulfan) or ingredient(DMSO etc.) * Participated in other clinical studies within 3 months prior to screening * Inoculated live vaccine within 6 weeks prior to screening * Pregnancy or breastfeeding women; Subjects or their sexual partners were unable to take medically recognized effective contraceptive measures during the 27-month study period * The subjects or their parents would not comply with the study procedures outlined in the protocol * The subjects received hydroxyurea or thalidomide or hypomethylating drugs within 3 months before hematopoietic stem cell collection * Patients considered to be ineligible for the study by the investigator for reasons other than the above

{'studyType': 'INTERVENTIONAL', 'phases': ['NA'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 3, 'type': 'ESTIMATED'}}

2024-01-23