Gene therapy for patients with β-thalassemia using modified stem cells

An Open, Multi-center, Phase I Clinical Study on the Safety and Efficacy of HGI-001 Injection in Patients with Transfusion-Dependent Β-Thalassemia.

This study is testing a new gene therapy using modified stem cells to see if it can help young people with β-thalassemia reduce their need for blood transfusions.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 8 (estimated)
• Ages: 6 Years to 35 Years
• Sex: All
• Sponsor: Shenzhen Hemogen (Industry-sponsored)
• Drugs / interventions: Ruxolitinib
• Locations: 3 sites (Guangxi and 2 other locations)
• Trial ID: NCT06655662 on ClinicalTrials.gov

What this trial studies

This Phase 1 clinical trial evaluates the safety and efficacy of autologous lentiviral-transduced CD34+ human hematopoietic stem cells in patients with transfusion-dependent β-thalassemia. Participants aged 6-35 will have their own stem cells collected and modified to restore β-globin expression using the LentiHBBT87Q system. After a conditioning regimen, these modified stem cells will be reinfused into the patients, who will be monitored for two years to assess outcomes. The study aims to provide insights into the potential of gene therapy for treating this genetic blood disorder.

Who should consider this trial

Good fit: Ideal candidates are transfusion-dependent β-thalassemia patients aged 6-35 with specific eligibility criteria regarding their health and transfusion history.

Not a fit: Patients with coexisting α-thalassemia or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce or eliminate the need for blood transfusions in β-thalassemia patients.

How similar studies have performed: Other studies using gene therapy approaches for β-thalassemia have shown promising results, indicating potential for success in this novel application.

Eligibility criteria

Inclusion Criteria:

1. Aged 6-35 years (inclusive), ICF can be provided by the patient and/or legal guardian;
2. Definitively diagnosed with severe TDT without genotype restriction (excluding patients with coexisting α-thalassemia), 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；
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. Serum ferritin level less than 5000μg/L, with moderate or lower iron overload in the heart and liver as indicated by magnetic resonance imaging (MRI T2\*), specifically liver MRI T2\* greater than 1.4ms and cardiac MRI T2\* greater than 10ms;
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. Having previously received gene therapy, gene editing therapy, or allogeneic hematopoietic stem cell transplantation;
3. Uncorrected bleeding disorder;
4. Uncontrolled epilepsy and mental illness;
5. Within the past 3 months prior to enrollment, the use of Luspatercept, Hydroxyurea, Ruxolitinib, Thalidomide, Decitabine, or Ara-c has been administered；
6. Psychoactive substance abuse, drug or alcohol abuse within 6 months prior to enrollment;
7. Patients with pulmonary hypertension who have not been given effective intervention;
8. Positive for anti-RBC antibodies in antibody screening;
9. Hepatitis B surface antigen (HBsAg) is positive and the HBV DNA copy number is greater than the upper limit of the normal value of the detection unit (those who are negative do not need to test for HBV DNA copy number), antibodies to Hepatitis C virus (HCV) are positive, antibodies to Human Immunodeficiency Virus (HIV) are positive, or antibodies to Treponema pallidum (TP-Ab) are positive (subjects who are positive due to vaccination are eligible for enrollment). Additionally, the results of Hepatitis B Virus (HBV) DNA testing, Hepatitis C Virus (HCV) RNA testing, Cytomegalovirus DNA testing, and Epstein-Barr Virus (EBV) DNA testing are abnormal；
10. Have or have had malignant tumors or myeloproliferative diseases or immunodeficiency disorders or autoimmune diseases;
11. Have a first-degree relative with a history of or suspected hereditary cancer (including but not limited to hereditary breast and ovarian cancer, nonpolyposis colorectal cancer, and adenomatous polyposis);
12. Severe bacterial, viral, fungal or parasitic infection;
13. 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 \<60 mL/(min·1.73m\^2);
14. WBC \< 3 × 10\^9/L and/or PLT \< 100 × 10\^9/L;
15. Has diabetes, abnormal thyroid functions or other endocrine disorder;
16. Participated in other interventional clinical studies within 4 weeks before the trial;
17. Poor adherence or other conditions that renders the subject unsuitable for participation as judged by the investigator.

Where this trial is running

Guangxi and 2 other locations

• Guangxi Medical University First Affiliated Hospital — Guangxi, China (Recruiting)
• Shenzhen Children's Hospital — Shenzhen, China (Recruiting)
• Shenzhen University General Hospital — Shenzhen, China (Recruiting)

Study contacts

• Principal investigator: Chao Liu, PHD — Shenzhen Hemogen
• Study coordinator: Haigang Sun

Conditions Β-thalassemia; β-thalassemia; Thalassemia; Genetic Diseases, Inborn; Hemoglobinopathies; Hematologic Diseases; Anemia; Anemia, Hemolytic