the Safety and Efficacy Evaluation of HGI-002 Injection in Patients With Transfusion-Dependent α-Thalassemia

Обзор

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

Вмешательства

• Биопрепарат α-globin restored autologous hematopoietic stem cells
  α-globin restored autologous hematopoietic stem cells modified with LentiHBA T\>C

Первичные конечные точки

• Overall response rate [Срок оценки: 0-24 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 100 d after transplantation [Срок оценки: Day 100]
• Overall survival rate during the clinical trial [Срок оценки: 0-24 months]
• HGI-002 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 cytology and bone marrow cytology within 24 months after reinfusion [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 [Срок оценки: 0-24 Months]
• Changes in cardiac iron load after reinfusion of HGI-002 injection [Срок оценки: 0-24 Months]
• Changes in liver iron load after reinfusion of HGI-002 injection [Срок оценки: 0-24 Months]
• Changes in serum ferritin after reinfusion of HGI-002 injection [Срок оценки: 0-24 Months]
• Changes use of iron chelation medications after reinfusion of HGI-002 injection [Срок оценки: 0-24 Months]

Критерии участия

Критерии включения

• Aged 12-35 years (inclusive), ICF can be provided by the patient and/or legal guardian;
• Definitively α- thalassemia 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-002 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

• PLA Joint Logistic Support Force No. 923 Hospital — Nanning

Публикации

• Yin X, Qian L, Dong G, Chen Y, Zhou Y, Yang B, Liao G, Sun H, Guo H, Zeng X, Zou H, Ye T, He J, Yao W, Ouyang W, Zhang X, Liu C. Successful gene therapy for transfusion-dependent alpha-thalassemia: a case report. Blood Adv. 2026 May 27:bloodadvances.2025019280. doi: 10.1182/bloodadvances.2025019280. Online ahead of print. PMID 42200456

Идентификаторы

NCT: NCT05851105 · HGI-002-C01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗