the Safety and Efficacy Evaluation of HGI-001 Injection in Patients With Transfusion-Dependent β-Thalassemia

Официальное название

the Safety and Efficacy Evaluation of HGI-001 Injection in Patients With Transfusion-Dependent β-Thalassemia(Child)

Обзор

This is an open label study to evaluate the safety and efficacy of β-globin Restored Autologous Hematopoietic Stem Cells in ß-Thalassemia Major Patients

Подробное описание

We will recruit ß-thalassaemia major patients and collect their autologous hematopoietic stem cells, which will be modified with the LentiHBBT87Q system to restore β-globin expression. After conditioning, the autologous hematopoietic stem cells with restored β-globin will be reinfused to the patients and followed up for two years to collect data.

Вмешательства

• Биопрепарат β-globin restored autologous hematopoietic stem cells
  β-globin-restored autologous hematopoietic stem cells modified with LentiHBBT87Q

Первичные конечные точки

• Overall response rate [Срок оценки: 24 months]
• Incidence and severity of AEs [Срок оценки: 0-24 months]
• Incidence of SAEs [Срок оценки: 0-24 months]
• Transplantation-related fatal and disabling events within day 100 after transplantation [Срок оценки: Day 100]
• Overall survival rate during the clinical trial [Срок оценки: 0-24 months]
• HGI-001 injection-related replicating lentivirus test [Срок оценки: 0-24 months]
• Change from baseline in Clonal variations containing specific viral integration sites [Срок оценки: 0-24 months]
• Number of patients with abnormal hematology and bone marrow cytology within 24 months after reinfusion, and percent of patients with abnormal RBC proliferation [Срок оценки: 0-24 months]

Вторичные конечные точки (11)

• Treatment response rate [Срок оценки: 12 Months]
• Percent of subjects with successful HSC engraftment [Срок оценки: 1 month]
• Change in transfusion volume or frequency [Срок оценки: 0-24 Months]
• Transfusion improvement rate [Срок оценки: 0-24 Months]
• Transfusion independence (TI) rate [Срок оценки: 0-24 Months]
• Transfusion-free survival [Срок оценки: 0-24 Months]
• Changes in VCN and exogenous adult HbAT87Q expression [Срок оценки: 0-24 Months]
• Changes in cardiac iron load after reinfusion of HGI-001 injection [Срок оценки: 0-24 Months]
• Changes in liver iron load after reinfusion of HGI-001 injection [Срок оценки: 0-24 Months]
• Changes in serum ferritin after reinfusion of HGI-001 injection [Срок оценки: 0-24 Months]
• Changes use of iron chelation medications after reinfusion of HGI-001 injection [Срок оценки: 0-24 Months]

Критерии участия

Критерии включения

• Aged 18-35 years (inclusive), ICF can be provided by the patient and/or legal guardian;
• Definitively diagnosed with severe TDT without genotype restriction, and a valid test report can be provided;
• Average transfusion volume > 100 mL/kg/year or transfusion frequency > 8 times/year within 2 years prior to enrollment, or has been definitively diagnosed with TDT;
• At least 3 months of full volume transfusion (verification of blood transfusion records can be provided) prior to screening, and Hb is maintained at ≥ 9.0 g/dL;
• Ferritin load < 3000 μg/L, cardiac and liver iron indicates moderate or lesser iron overload; records of iron chelation treatments within 3 months before screening (including prescription or receipt) can be provided;
• Acceptable organ functions (including heart, liver, kidney, lung and coagulation functions), stable disease condition, and suitable for busulfan pre-treatment and hematopoietic stem cell (HSC) transplantation as judged by the investigator;
• Meets follow-up requirements, adheres to treatment arrangements, and is able to return to the hospital regularly to undergo various examinations within 2 years after reinfusion of HGI-001 injection.

Критерии исключения

• Patients with fully HLA-matched donors;
• Received allogeneic transplantation, which needs to be weighed and evaluated by an expert committee; received other gene therapies;
• Have previously undergone splenectomy;
• Uncorrected bleeding disorder;
• Uncontrolled epilepsy and mental illness;
• Received hydroxyurea, ruxolitinib, decitabine, or cytarabine within 3 months prior to enrollment;
• Psychoactive substance abuse, drug or alcohol abuse within 6 months prior to enrollment;
• Patients with pulmonary hypertension who have not been given effective intervention;
• Persistent toxicity (≥ CTCAE grade 2) induced by previous treatment;
• Positive for anti-RBC antibodies in antibody screening;
• Positive for hepatitis B surface antigen (HBsAg) and HBV DNA copy number > upper limit of normal (ULN) (HBV DNA test not required for patients negative for HBsAg), positive for hepatitis C virus (HCV) antibody, positive human immunodeficiency virus (HIV), or positive for Treponema pallidum antibody (TP-Ab) (subjects who are positive for the antibody due to vaccination can be enrolled). In certain clinical environments/regions, subjects who are positive for other tests can also be excluded from the trial, such as, human lymphocytic virus-1 (HTLV-1) or -2 (HTLV-2), tuberculosis, and toxoplasmosis.
• Has or has had malignant tumors or myeloproliferative disease or immunodeficiency disease;
• Immediate family member with or suspected of having a familial cancer (including but not limited to hereditary breast and ovarian cancers, nonpolyposis colorectal cancer, and adenomatous polyposis);
• Severe bacterial, viral, fungal or parasitic infection;
• Other illnesses which render the subject unsuitable for participation (e.g., severe liver, kidney or heart disease); Definition of severe liver and kidney disease: a. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin > 3 × ULN; b. Liver magnetic resonance imaging (MRI) indicates significant cirrhosis; c. Liver biopsy indicates cirrhosis, severe fibrosis or active hepatitis (liver biopsy is only performed when liver MRI indicates active hepatitis and significant fibrosis without evidence for cirrhosis); d. Creatinine clearance < 30% of normal;
• WBC < 3 × 109/L and/or PLT < 100 × 109/L;
• Has diabetes, abnormal thyroid functions or other endocrine disorder;
• Participated in other interventional clinical studies within 4 weeks before the trial;
• Poor adherence or other conditions that renders the subject unsuitable for participation as judged 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

• Shenzhen University General Hospital — Шэньчжэнь

Идентификаторы

NCT: NCT05864170 · HGI-001-CTP

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗