Clinical trial NCT05864170: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: β-thalassemia
Lead sponsor: Shenzhen Hemogen
Sponsor class: INDUSTRY
First posted: 2023-05-18
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility criteria: Inclusion Criteria:

1. Aged 18-35 years (inclusive), ICF can be provided by the patient and/or legal guardian;
2. Definitively diagnosed with severe TDT without genotype restriction, and a valid test report can be provided;
3. 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;
4. 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;
5. 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;
6. 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;
7. 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:

1. Patients with fully HLA-matched donors;
2. Received allogeneic transplantation, which needs to be weighed and evaluated by an expert committee; received other gene therapies;
3. Have previously undergone splenectomy;
4. Uncorrected bleeding disorder;
5. Uncontrolled epilepsy and mental illness;
6. Received hydroxyurea, ruxolitinib, decitabine, or cytarabine within 3 months prior to enrollment;
7. Psychoactive substance abuse, drug or alcohol abuse within 6 months prior to enrollment;
8. Patients with pulmonary hypertension who have not been given effective intervention;
9. Persistent toxicity (≥ CTCAE grade 2) induced by previous treatment;
10. Positive for anti-RBC antibodies in antibody screening;
11. 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.
12. Has or has had malignant tumors or myeloproliferative disease or immunodeficiency disease;
13. 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);
14. Severe bacterial, viral, fungal or parasitic infection;
15. 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;
16. WBC \< 3 × 109/L and/or PLT \< 100 × 109/L;
17. Has diabetes, abnormal thyroid functions or other endocrine disorder;
18. Participated in other interventional clinical studies within 4 weeks before the trial;
19. Poor adherence or other conditions that renders the subject unsuitable for participation as judged by the investigator.

Primary outcomes:
measure: Overall response rate
timeFrame: 24 months
measure: Incidence and severity of AEs
timeFrame: 0-24 months
measure: Incidence of SAEs
timeFrame: 0-24 months
measure: Transplantation-related fatal and disabling events within day 100 after transplantation
timeFrame: Day 100
measure: Overall survival rate during the clinical trial
timeFrame: 0-24 months
measure: HGI-001 injection-related replicating lentivirus test
timeFrame: 0-24 months
measure: Change from baseline in Clonal variations containing specific viral integration sites
timeFrame: 0-24 months
measure: Number of patients with abnormal hematology and bone marrow cytology within 24 months after reinfusion, and percent of patients with abnormal RBC proliferation
timeFrame: 0-24 months
Secondary outcomes:
measure: Treatment response rate
timeFrame: 12 Months
measure: Percent of subjects with successful HSC engraftment
timeFrame: 1 month
measure: Change in transfusion volume or frequency
timeFrame: 0-24 Months
measure: Transfusion improvement rate
timeFrame: 0-24 Months
measure: Transfusion independence (TI) rate
timeFrame: 0-24 Months
measure: Transfusion-free survival
timeFrame: 0-24 Months
measure: Changes in VCN and exogenous adult HbAT87Q expression
timeFrame: 0-24 Months
measure: Changes in cardiac iron load after reinfusion of HGI-001 injection
timeFrame: 0-24 Months
measure: Changes in liver iron load after reinfusion of HGI-001 injection
timeFrame: 0-24 Months
measure: Changes in serum ferritin after reinfusion of HGI-001 injection
timeFrame: 0-24 Months
measure: Changes use of iron chelation medications after reinfusion of HGI-001 injection
timeFrame: 0-24 Months
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: Shenzhen University General Hospital
state: Guangdong
Study officials:
affiliation: Shenzhen Hemogen
name: Chao Liu, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Shenzhen University General Hospital
name: Li Yu
role: PRINCIPAL_INVESTIGATOR
References: