Safety and Efficacy of the Lentiviral Vector in Gene Therapy of Beta-thalassemia Patients

Официальное название

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

Обзор

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 transfusion-dependent β-thalassemia.

Вмешательства

• Генная терапия KL003 cell injection Drug Product
  No conditioning regimen for transfusion of auto-HSC transduced with lentiviral vector encoding βA-T87Q-globin gene

Первичные конечные точки

• The number, frequency and severity of adverse events (AE) after reinfusion of KL003 drug products [Срок оценки: within 6 months]
• The proportion of participants who meet the definition of transfusion independence (TI) for at least 6 months [Срок оценки: Up to 24 months post transplant]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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:

• 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;
• History of bridging fibrosis, cirrhosis;
• Left ventricular ejection fraction <45%;
• New York Heart Association (NYHA) class III or IV congestive heart failure;
• Severe arrhythmia requiring medical treatment;
• Uncontrolled hypertension or unstable angina pectoris;
• Myocardial infarction or bypass or stent surgery within 12 months before drug administration;
• Valvular disease with clinical significance;
• Baseline calculated eGFR<60mL/min/1.73m2;
• Pulmonary function: FEV1/FVC<60% and/or diffusion capacity of carbon monoxide (DLco) <60% of prediction;
• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Institute of Hematology & Blood Diseases Hospital — Тяньцзинь

Идентификаторы

NCT: NCT06219239 · IIT2023084

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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