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

NCT ID: NCT05864170

Last Updated: 2024-11-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-27
• Study Completion Date: 2025-12-30

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.

Conditions

β-thalassemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental

Three transfusion-dependent β-thalassaemia subjects aged 18-35 years will be reinfused with β-globin restored autologous hematopoietic stem cells modified with LentiHBBT87Q

Group Type: EXPERIMENTAL

β-globin restored autologous hematopoietic stem cells

Intervention Type: BIOLOGICAL

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

Interventions

β-globin restored autologous hematopoietic stem cells

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

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shenzhen Hemogen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chao Liu, PHD

Role: PRINCIPAL_INVESTIGATOR

Shenzhen Hemogen

Li Yu

Role: PRINCIPAL_INVESTIGATOR

Shenzhen University General Hospital

Locations

Shenzhen University General Hospital

Shenzhen, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Haigang Sun

Role: CONTACT

sunhaigang@genomics.cn

13823168465

Facility Contacts

Haigang Sun

Role: primary

sunhaigang@genomics.cn

13823168465

Other Identifiers

HGI-001-CTP

Identifier Type: -

Identifier Source: org_study_id