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

Early Phase 1

Recruiting

• Conditions: α-thalassemia
• Interventions: Biological: α-globin restored autologous hematopoietic stem cells

• Registration Number: NCT05851105
• Lead Sponsor: Shenzhen Hemogen

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2022-10-08
• Study First Submitted: 2023-02-28
• Study First Submitted QC: 2023-05-06
• Study First Posted: 2023-05-09
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-26
• Last Update Posted: 2024-11-28
• Primary Completion: 2026-12-30
• Study Completion: 2026-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 3

Inclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental	α-globin restored autologous hematopoietic stem cells	Three transfusion-dependent α-thalassaemia subjects aged 12-35 years will be reinfused with α-globin restored autologous hematopoietic stem cells modified with LentiHBA T\>C

Primary Outcome Measures

Name	Time	Method
Overall response rate	0-24 months	Percent of patients with average VCN \> 0.1 in peripheral blood mononuclear cells
Incidence and severity of AEs	0-24 months	The number and the percentage of adverse events related to transplantation will be summarized according to NCI CTCAE 5.0
incidence of SAEs	0-24 months	The number of SAE related to transplantation will be summarized according to NCI CTCAE 5.0
Transplantation-related fatal and disabling events within 100 d after transplantation	Day 100	Transplantation-related fatal and disabling events
HGI-002 injection-related replicating lentivirus test	0-24 months	The percentage of RCL should be negative in the 24 months after transplant
Overall survival rate during the clinical trial	0-24 months	Number of patients alive through the whole trial will be record
Change from baseline in Clonal variations containing specific viral integration sites	0-24 months	Evaluation of the percentage of participants without abnormal clonal proliferation and polyclonal engraftment at baseline, 6, 12, 18 and 24 months after transplant. More than 1000 VIS retrieved from peripheral blood should be checked.
Number of patients with abnormal hematology cytology and bone marrow cytology within 24 months after reinfusion	0-24 months	Number of patients with abnormal hematology cytology and bone marrow cytology

Secondary Outcome Measures

Name	Time	Method
Treatment response rate	12 Months	Percent of patients with average VCN \> 0.1 in PBMCs
Percent of subjects with successful HSC engraftment	1 month	Criteria for successful engraftment: Absolute neutrophil count \> 0.5 × 10 9 /L for 3 consecutive days; platelet count is maintained at \> 20 × 10 9 /L for 7 consecutive days without platelet transfusion
Transfusion improvement rate	0-24 Months	Percent of subjects with ≥ 30% decrease in the average annual (0-12 months, 12-24 months) transfusion volume or frequency from baseline after reinfusion of HGI-002 injection
Change in transfusion volume or frequency	0-24 Months	Change in average annual transfusion volume or frequency from baseline or change in percentage
Transfusion independence (TI) rate	0-24 Months	Percent of subjects who do not require transfusion for at least 12 consecutive months after reinfusion of HGI-002 injection and have a weighted average Hb of ≥ 9.0 g/dL
Transfusion-free survival	0-24 Months	the time when a subject meets the TI criteria and maintains transfusion-free survival
Changes in VCN	0-24 Months	Vector copy number
Changes in cardiac iron load after reinfusion of HGI-002 injection	0-24 Months	T2 MRI
Changes in liver iron load after reinfusion of HGI-002 injection	0-24 Months	T2 MRI
Changes in serum ferritin after reinfusion of HGI-002 injection	0-24 Months	serum ferritin
Changes use of iron chelation medications after reinfusion of HGI-002 injection	0-24 Months	iron chelation medications

Trial Locations

Locations (1)

PLA Joint Logistic Support Force No. 923 Hospital; 🇨🇳 Nanning, Guangxi, China