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

ß-thalassemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05864170
• Other study ID #: HGI-001-CTP
• Status: Recruiting
• Phase: Early Phase 1
• Start date: May 27, 2022
• Est. completion date: August 2025

Study information

• Verified date: May 2023
• Source: Shenzhen Hemogen
• Contact: Haigang Sun
• Phone: 13823168465
• Email: sunhaigang[@]genomics.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3
• Est. completion date: August 2025
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

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.

Related Conditions & MeSH terms

• beta-Thalassemia
• ß-thalassemia
• Thalassemia

Intervention

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

Locations

Country	Name	City	State
China	Shenzhen University General Hospital	Shenzhen	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Shenzhen Hemogen

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate	Percent of patients with average VCN > 0.1 in peripheral blood mononuclear cells (PBMCs) and average expression of exogenous adult hemoglobin HbAT87Q > 2.0 g/dL	24 months
Primary	Incidence and severity of AEs	The number and the percentage of adverse events related to transplantation will be summarized according to NCI CTCAE 5.0	0-24 months
Primary	Incidence of SAEs	The number of SAE related to transplantation will be summarized according to NCI CTCAE 5.0	0-24 months
Primary	Transplantation-related fatal and disabling events within day 100 after transplantation	Transplantation-related fatal and disabling events	Day 100
Primary	Overall survival rate during the clinical trial	Number of patients alive through the whole trial will be record	0-24 months
Primary	HGI-001 injection-related replicating lentivirus test	The percentage of RCL should be negative in the 24 months after transplant	0-24 months
Primary	Change from baseline in Clonal variations containing specific viral integration sites	Evaluation of the percentage of participants without abnormal clonal proliferation and polyclonal engraftment at 6, 12, 18 and 24 months after transplant. More than 1000 VIS retrieved from peripheral blood should be checked.	0-24 months
Primary	Number of patients with abnormal hematology and bone marrow cytology within 24 months after reinfusion, and percent of patients with abnormal RBC proliferation	Number of patients with abnormal hematology and bone marrow cytology	0-24 months
Secondary	Treatment response rate	Percent of patients with average VCN > 0.1 in PBMCs and average expression of exogenous adult hemoglobin HbAT87Q > 2.0 g/dL after reinfusion of HGI-001 injection	12 Months
Secondary	Percent of subjects with successful HSC engraftment	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	1 month
Secondary	Change in transfusion volume or frequency	Change in average annual transfusion volume or frequency from baseline or change in percentage	0-24 Months
Secondary	Transfusion improvement rate	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-001 injection	0-24 Months
Secondary	Transfusion independence (TI) rate	Percent of subjects who do not require transfusion for at least 12 consecutive months after reinfusion of HGI-001 injection and have a weighted average Hb of = 9.0 g/dL	0-24 Months
Secondary	Transfusion-free survival	the time when a subject meets the TI criteria and maintains transfusion-free survival	0-24 Months
Secondary	Changes in VCN and exogenous adult HbAT87Q expression	Vector copy number	0-24 Months
Secondary	Changes in cardiac iron load after reinfusion of HGI-001 injection	T2 MRI	0-24 Months
Secondary	Changes in liver iron load after reinfusion of HGI-001 injection	T2 MRI	0-24 Months
Secondary	Changes in serum ferritin after reinfusion of HGI-001 injection	serum ferritin	0-24 Months
Secondary	Changes use of iron chelation medications after reinfusion of HGI-001 injection	iron chelation medications	0-24 Months