Gene Therapy for Patients With Transfusion-Dependent β-Thalassemia

An Open Label Study Evaluating the Safety and Efficacy of HGI-001 Injection in Patients With Transfusion-Dependent β-Thalassemia

Thalassemia is a group of recessively inherited hemoglobin disorders characterized by reduced or no production of hemoglobin and chronic anemia of varying severity. Severe β-thalassemia is transfusion-dependent thalassemia (TDT) and requires life-long transfusion, iron overload is a common complication of TDT. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative option currently available for TDT, but it carries significant acute and long-term risks. In this study, the autologous HSCT-based gene therapy (referred to as "gene therapy for thalassemia, " by using HGI-001) is based on the principle that the autologous haemopoietic stem cells (HSCs) collected from the patient him/herself are transduced outside human body, which will restore the function of RBCs, so as to achieve the effect of treating or even curing thalassemia. Currently data suggests that gene therapy for TDT patients has shown remarkable therapeutic effects, avoiding immune rejection, and is widely accepted by the medical community, positioning it as a highly promising treatment approach. To date, the efficacy and safety of HGI-001 have been evaluated through both in vitro and in vivo studies. In an early-phase clinical study of HGI-001 conducted in China, five patients achieved transfusion-independent post-treatment. Among them, four have maintained this state for over two years, with the longest duration reaching 3.5 years. The study noted no severe adverse events. The long-term safety and efficacy of HGI-001 continue to be under active surveillance.

Study Overview

• Status: Not yet recruiting
• Conditions: Beta Thalassemia Transfusion Dependent
• Intervention / Treatment: Drug: HGI-001 Injection

Detailed Description

This is a single-arm, open-label, single-dose, single site study in approximately 6 subjects ≥12 and ≤45 years of age with TDT. Subjects must have TDT with a transfusion history of at least 100mL/kg/year of packed red blood cells (pRBCs) or 8 transfusions of pRBCs per year in the past 2 years before enrollment.

Stage 1: Screening to determine eligibility for treatment: Subjects with previously known β0/β0 or non-β0/β0 genotypes are eligible for screening.

Stage 2: Autologous CD34+ cell collection, HGI-001 Injection manufacture and disposition: Each subject will undergo HSC mobilization with a granulocyte-colony stimulating factor (G-CSF) and plerixafor. Peripheral blood mononuclear cells (PBMCs) will be collected by apheresis. A total of 2 mobilization cycles may be performed if needed and each mobilization cycle may include up to 3 days for apheresis.

Stage 3: Myeloablative conditioning and infusion of HGI-001 Injection (Day 0)

: the subject will undergo myeloablative conditioning with busulfan. After completion of the 4-day course of busulfan, there must be a minimum of 48 hours of washout period before administration of HGI-001 Injection. On study Day 0, after thawing, the HGI-001 Injection will be administered via intravenous (IV) infusion at a dose of >4.0 × 106 CD34+ cells/kg.

Stage 4: Follow-up, through engraftment and up to 12 months after HGI-001 Infusion: Subjects will be followed up daily in the transplant unit for adverse events (AEs), and laboratory parameters will be followed up to monitor bone marrow engraftment. The subject will be discharged from the transplant unit once the subject is considered clinically stable.

The goal during the follow-up period is to maintain hemoglobin (Hb) ≥9 g/dL. Transfusions should be avoided for patients with Hb ≥9 g/dL, unless the transfusion need is medically justified (e.g., as a pre-requirement for surgery).

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chi Kong Li, MBBS MD; Phone Number: +85235051019; Email: ckli@cuhk.edu.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects between 12 and 45 years of age at the time of consent and are able to provide written informed consent.
2. Diagnosis of TDT, also known as β-thalassemia major, without genotype restriction, and a valid test report can be provided.
3. A history of at least 100 mL/kg/year of pRBCs transfusion or ≥ 8 transfusions of pRBCs per year for previous 2 years.
4. Sufficient blood transfusion for at least 3 months before screening (transfusion records can be provided), and Hb is maintained ≥9.0 g/dL before each transfusion.
5. The level of ferritin <5000ng/mL; Cardiac magnetic resonance imaging (MRI) T2 and liver MRI T2 findings suggest iron overload at a moderate level or below.
6. Clinically stable, and eligible for autologous hematopoietic stem cell transplant (auto-HSCT).
7. Adequate organ function for the conditioning with busulfan.

Exclusion Criteria:

1. Uncorrected bleeding disorder;
2. Uncontrolled epilepsy or mental disorders;
3. Received hydroxyurea, ruxolitinib, decitabine, or cytarabine within 3 months prior to enrollment;
4. Usage of psychoactive substance, drug, or alcohol abuse within six months prior to screening.
5. Pulmonary hypertension without effective intervention.
6. Persistent toxicity (≥ CTCAE grade 2) induced by previous treatment.
7. Positive for anti-RBC antibodies.
8. 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, unless HCV RNA is negative (HCV RNA-negative subjects are not excluded), 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).
9. Has or has had malignant tumors or myeloproliferative disease or immunodeficiency disease;
10. Clinically significant and active bacterial, viral, fungal, or parasitic infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: single arm study of gene therapy; gene therapy product will be used to correct the genetic defect of thalassemia major	Drug: HGI-001 Injection; HGI-001 Injection is the transduction of autologous CD34+ HSPCs by the lentiviral vector, named LentiHBBT87Q

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
achieve transfusion independence (TI)for at least ≥12 months after HGI-001 Injection infusion	Subjects achieve transfusion independence (TI), which is defined as a weighted average Hb ≥9 g/dL without any pRBC transfusions at any time for a continuous period of ≥12 months during the study after HGI-001 Injection infusion	12 month after injection of study drug

Collaborators and Investigators

• Sponsor: Prince of Wales Hospital, Shatin, Hong Kong

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: July 17, 2026
• First Submitted That Met QC Criteria: July 17, 2026
• First Posted (Actual): July 23, 2026

Study Record Updates

• Last Update Posted (Actual): July 23, 2026
• Last Update Submitted That Met QC Criteria: July 17, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: transfusion dependent, beta thalassemia, gene therapy
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Thalassemia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; beta-Thalassemia
• Other Study ID Numbers: CREC2025.659

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: patients' age, sex, genotypes, post-treatment outcome
• IPD Sharing Time Frame: five years
• IPD Sharing Access Criteria: researchers in the field
• IPD Sharing Supporting Information Type: ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No