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

Official title

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

Overview

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

Detailed description

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.

Interventions

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

Primary outcome measures

• Overall response rate [Time frame: 24 months]
• Incidence and severity of AEs [Time frame: 0-24 months]
• Incidence of SAEs [Time frame: 0-24 months]
• Transplantation-related fatal and disabling events within day 100 after transplantation [Time frame: Day 100]
• Overall survival rate during the clinical trial [Time frame: 0-24 months]
• HGI-001 injection-related replicating lentivirus test [Time frame: 0-24 months]
• Change from baseline in Clonal variations containing specific viral integration sites [Time frame: 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 [Time frame: 0-24 months]

Secondary outcome measures (11)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shenzhen University General Hospital — Shenzhen

Identifiers

NCT: NCT05864170 · HGI-001-CTP

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗