Safety and Efficacy of Gene Modified Autologous Hematopoietic Stem Cells to Treat Transfusion-dependent Beta-thalassemia

Официальное название

Safety and Efficacy of Lentiviral Vector Transduction of β-globin Genetically Modified Autologous CD34+ Hematopoietic Stem Cells in Patients With Transfusion-dependent β-thalassemia

Обзор

This study will be intented to evaluate the safety, tolerability, and engraftment efficacy after myeloablative preconditioning and transplantation of autologous CD34+ hematopoietic stem cells transduced with a lentiviral vector encoding the human βA-T87Q-globin gene in patients with transfusion-dependent (TDT) β-thalassemia.

Подробное описание

This is an open-label, single-dose study of BD211 in patients with transfusion-dependent β-thalassemia aged 3 to 18 years. It is estimated that 10 subjects will be enrolled. BD211 is a gene modified gene therapy product designed to produce healthy β-globin in red blood cells in beta-thalassemia patients. The total follow-up duration was 24 months, the safe endpoints and effectiveness endpoints will be used to assess the safety and efficacy profiles in patients with transfusion-dependent β-thalassemia.

Вмешательства

• Генная терапия BD211
  Genetically modified CD34+ autologous stem cells were transfused intravenously with single dosing.

Первичные конечные точки

• Percentage of treated participants with Transfusion-Dependent β-Thalassemia (TDT) who achieved transfusion independence (TI) for at least 6 months [Срок оценки: 24 months]

Вторичные конечные точки (12)

• Hb (g/dL) level between 12 and 24 months after BD211 treatment compared with baseline Hb level [Срок оценки: 24 months]
• Parameters of efficacy related to TI achievement after BD211 treatment [Срок оценки: 24 months]
• Parameters of efficacy related to reduced blood transfusion after BD211 treatment [Срок оценки: 24 months]
• Parameters of iron overload after BD211 treatment [Срок оценки: 24 months]
• Parameters of growth and development after BD211 treatment [Срок оценки: 24 months]
• Change in quality of life from baseline [Срок оценки: 24 months]
• Total hospitalizing days at 12, and 24 months (discharge after transplant) [Срок оценки: 24 months]
• Measurement of PD/PK parameters [Срок оценки: 24 months]
• Neutrophil engraftment and platelet engraftment [Срок оценки: 24 months]
• Transplant-related mortality in 3 months and 12 months [Срок оценки: 12 months]
• Overall survival [Срок оценки: 24 months]
• RCL incidence [Срок оценки: 24 months]

Критерии участия

Критерии включения

• Ages 3 to 18 years old, including:

The parents or legal guardians must be able to understand and provide ICFs. If available, it is strongly recommended that children aged ≥8 years in treatment decisions and obtain written ICFs and be clearly documented; Diagnosed as Transfusion Dependent β-thalassemia with any genotype (β0, β+, βE/β0, βS/S, βS/β0, βS/β+), confirmed the Hb analysis. No alfa chain genetic abnormalities. Subjects must stabilize and maintain an appropriate iron chelation regimen. Transfusion-dependent types are defined as requiring at least 100 mL/kg/ year of red blood cells (pRBCs).

• No eligiblity for allogeneic hematopoietic stem cell transplantation.
• The treatment of erythrocyte maturation agent luspatercept cannot be financially supported.
• The subjects' parents/legal guardians must be willing and able to follow the study procedures in the study protocol.
• Good organs' functions.
• Having complete medical records including a history of blood transfusions testified subject received treatment and followed up for at least two years prior to screening .

Критерии исключения

• Availability of voluntary, fully HLA-matched hematopoietic cell donors, unless recommended for inclusion by the Monitoring Committee.
• HIV-1 and HIV-2 were positive, and / or HTLV-1, HTLV-2 and VSV-G antibodies were positive.
• An active bacterial, viral, fungal or parasitic infection.
• Contraindicated for the extraction of bone marrow under anesthesia.
• Any malignancy, myeloproliferative, or immunodeficient disease and relevant medical history.
• Peripheral blood white blood cell (WBC) count < 3×10\^9/L or platelet count < 120×10\^9/L.
• A history of allo-transplantation.
• Erythropoietin was used within 3 months prior to HSC cell collection.
• Immediate family members with known or suspected familial cancer syndromes (including but not limited to breast, colorectal, ovarian, prostate, and pancreatic cancers).
• Subjects with a diagnosis of major mental illness may had a serious disability to participate in the study.
• Active recurrent malaria.
• Had autoimmune diseases that may make blood transfusions difficult.
• History of major organ injury including:

Liver disease, transaminase > 3 times the upper limit of normal. (If the liver biopsy does not reveal evidence of widespread bridging fibrosis, cirrhosis, or acute hepatitis, this indicator will not be used as a criterion for the exclusion); Widely bridging fibrosis, histopathological evidence of acute hepatitis or cirrhosis showed in liver biopsy Heart disease, left ventricular ejection fraction < 25%; Kidney disease, creatinine clearance < 30% normal level; Of severe iron overload, confirmed by the study doctor; An heart MRI detection of T2 \* < 10 ms; Significant pulmonary hypertension needing clinical medical intervention.

• There are bleeding diseases that have not been cured.
• The subject involved with another clinical study in a 30-day screening period.
• Allergic to the research drug and its excipients.
• Prior treatment with any type of gene and/or cell therapy.
• As assessed by the investigator, the subjects or their parents are unable to comply well with the study procedures per protocol.
• Hydroxyurea treatment within 3 months prior to hematopoietic stem cell collection.
• Had diseases that interfere with hematopoietic stem cells collections.
• Any other conditions being ineligible for HSC transplantation determined by the investigator.

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

• Shanghai Children's Medical Centre — Шанхай

Идентификаторы

NCT: NCT05773729 · BD-TDT-211003

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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