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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Beta-Thalassemia
• Intervention / Treatment: Drug: Vebeglogene autotemcel

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 3
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

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

Description

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.

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: Vebeglogene autotemcel; One-time infusion of≥5×10^6/kg beta-globin lentiviral vector transduced HSCs	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.; Other Names: Beta-globin lentiviral vector transduced autologous HSCs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Collaborators and Investigators

• Sponsor: Lantu Biopharma

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: March 6, 2024
• First Submitted That Met QC Criteria: March 6, 2024
• First Posted (Actual): March 13, 2024

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Thalassemia; beta-Thalassemia
• Other Study ID Numbers: LT02-101

Drug and device information, study documents

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