An Open-label Study of a Gene Therapy Product in Beta-Thalassemia

Beta-Thalassemia Clinical Trial

Official title:

An Open-label Clinical Trial of Ex Vivo Beta-globin Lentiviral Vector Transduction of Autologous CD34+HSCs (Vebeglogene Autotemcel) for the Treatment of Beta-thalassemia Patients

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06308159
• Other study ID #: LT02-101
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: April 1, 2024
• Est. completion date: April 1, 2027

Study information

• Verified date: March 2024
• Source: Lantu Biopharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an interventional study to evaluate the safety and efficacy of autologous Hematopoietic Stem Cells (HSCs) transduced with lentiviral vector encoding functional hemoglobin subunit beta (HBB) gene in patients with transfusion-dependent beta-thalassemia.

Description:

The participant's autologous HSCs will be transduced with the self-inactivating lentiviral vector, carrying the functional HBB gene. Study duration per participant is approximately 27 months including an approximately 30-day screening/baseline period, an approximately 40-day mobilization and product manufacture, an approximately 10-day myeloablative conditioning, 1 treatment day, and an approximately 24-month study observation period. The endpoints will be used to assess the safety and efficacy profiles in patients with transfusion-dependent beta-thalassemia.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 3
• Est. completion date: April 1, 2027
• Est. primary completion date: April 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 35 Years

Eligibility

Inclusion Criteria:

• Patients or parent(s)/legal guardian(s) willing and able to complete the informed consent process and comply with study procedures and visit schedules.
• Diagnosis of beta-thalassemia and a history of RBCs transfusions.
• Documented baseline, or pretransfusion, Hb=7 g/dL.
• Availability of an adequate and well-documented transfusion history.

Exclusion Criteria:

• Active bacterial, viral, fungal, or parasitic infection.
• A white blood cell (WBC) counts<3×10^9/L, and/or platelet counts<100×10^9/L not related to hypersplenism.
• Uncorrected bleeding disorder.
• Presence of severe diseases that judged not compatible with the study procedures, such as severe hepatic disease, kidney disease, lung disease, and/or cardiovascular disease.
• Uncontrolled seizure disorder.
• Any evidence of severe iron overload that, in the investigator's opinion, warrants exclusion.
• Prior autologous hematopoietic stem cell transplantation.
• Prior receipt of gene therapy.

Related Conditions & MeSH terms

• Beta-Thalassemia
• Thalassemia

Intervention

Drug:
• Vebeglogene autotemcel
Autologous HSCs transduced with self-inactivating lentiviral vector encoding functional HBB gene and resuspended in cryopreservative solution in the final immediate container for the intended medical use.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Lantu Biopharma

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time and duration of the subject's hemoglobin (Hb)=9.0 g/dL without receiving red blood cell infusion		From baseline to Month 24
Secondary	The prevalence and severity of adverse events (AEs) and serious adverse events (SAEs)	Participants are monitored for safety from baseline up to the end of the follow-up period.	From baseline to Month 24
Secondary	The reduction of red blood cells (RBCs) transfusion requirement after product infusion compared to previous transfusion records	The annual number of RBCs transfusions prior to product infusion will be compared to the annual number of RBCs transfusions post-infusion, and the requirement reduction duration should be reported.	From infusion to Month 24
Secondary	Number of days required to achieve successful neutrophil and platelet engraftment	Neutrophil engraftment is defined as the time to the first of 3 consecutive days of absolute neutrophil counts (ANC)=0.5×10^9/L post-infusion without transfusion. Platelet engraftment is defined as the time to the first of 3 consecutive days of platelet values=20×10^9/L post-infusion without transfusion.	From infusion to Month 24
Secondary	Vector copy number (VCN) in peripheral blood over time	Quantification of the lentiviral vector copy number in individual peripheral blood cells will be conducted to measure the transduction of HSCs.	From baseline to Month 24