Evaluating a new injection for patients with transfusion-dependent β-thalassemia

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

This study is testing a new injection made from patients' own modified stem cells to see if it can help young adults with severe β-thalassemia reduce their need for blood transfusions.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 3 (estimated)
• Ages: 18 Years to 35 Years
• Sex: All
• Sponsor: Shenzhen Hemogen (Industry-sponsored)
• Drugs / interventions: ruxolitinib
• Locations: 1 site (Shenzhen, Guangdong)
• Trial ID: NCT05864170 on ClinicalTrials.gov

What this trial studies

This open-label study aims to assess the safety and efficacy of β-globin restored autologous hematopoietic stem cells in patients diagnosed with β-thalassemia major. Participants aged 18-35 will have their own hematopoietic stem cells collected and modified using the LentiHBBT87Q system to restore β-globin expression. After a conditioning regimen, these modified cells will be reinfused into the patients, who will be monitored for two years to gather data on outcomes and safety. The study focuses on patients with severe transfusion-dependent β-thalassemia who meet specific eligibility criteria.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 18-35 with a definitive diagnosis of severe transfusion-dependent β-thalassemia.

Not a fit: Patients outside the age range of 18-35 or those with severe organ dysfunction may not benefit from this study.

Why it matters

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

How similar studies have performed: Other studies involving gene therapy for β-thalassemia have shown promising results, indicating potential for success with this approach.

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.

Where this trial is running

Shenzhen, Guangdong

• Shenzhen University General Hospital — Shenzhen, Guangdong, China (Recruiting)

Study contacts

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

Conditions β-thalassemia