Safety and Efficacy Evaluation of β-globin Restored Autologous Hematopoietic Stem Cells in β-thalassemia Major Patients

This is an open label study to evaluate the safety and efficacy of β-globin Restored Autologous Hematopoietic Stem Cells in ß-Thalassemia Major Patients

Study Overview

• Status: Recruiting
• Conditions: β-thalassemia
• Intervention / Treatment: Biological: β-globin restored autologous hematopoietic stem cells

Detailed Description

We will recruit ß-thalassaemia major patients and collect their autologous hematopoietic stem cells, which will be modified with the LentiHBBT87Q system to restore β-globin expression. After conditioning, the autologous hematopoietic stem cells with restored β-globin will be reinfused to the patients and followed up for two years to collect data.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Haigang Sun; Phone Number: 13823168465; Email: sunhaigang@genomics.cn

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518083
      • Recruiting
      • Shenzhen Children's Hospital
      • Contact: Haigang Sun; Phone Number: 13823168465; Email: sunhaigang@genomics.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 16 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 8-16 years old. Subject and/or subject's legal guardian fully understand and voluntarily sign informed consent;
• Clinically diagnosed as transfusion-dependent β-thalassemia major;
• With sufficient RBC infusion, subjects must maintain hemoglobin ≥9g/dL, serum ferritin threshold ≤ 3000 ng/mL and the liver iron overload mild or absent for at least 3 months before mobilization of hematopoietic stem cell;
• Follow the arrangements for treatment and regular medical checks within two years post-transplantation

Exclusion Criteria:

• The physical condition does not meet the requirements for hematopoietic stem cell mobilization and transplantation myeloablation;
• Received gene therapy and allogeneic HSCT in the past.
• Have an available HLA matched donor.
• Enrolling in another clinical trial.
• Other unsuitable conditions identified by doctors.

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: Experimental; Ten transfusion-dependent β-thalassaemia subjects aged 8-16 years will be reinfused with β-globin-restored autologous hematopoietic stem cells modified with LentiHBBT87Q.	Biological: β-globin restored autologous hematopoietic stem cells; β-globin-restored autologous hematopoietic stem cells modified with LentiHBBT87Q

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and severity of adverse events (AEs) and serious adverse events (SAEs)	The number and the percentage of adverse events related to transplantation in 100 days will be summarized according to NCI CTCAE 5.0	0-100 days
Overall survival	Number of patients alive through the whole trial will be record	0-24 months
Proportion of engraftment	Neutrophil count [ANC] >=500 /mm3 for 3 consecutive days and platelet count [PLT] >20,000/mm3 for7 consecutive days	0-24 months
Replication competent lentivirus (RCL)	The percentage of RCL should be negative in the 24 months after transplant	0-24 months
Dynamics of viral integration sites (VIS)	Evaluation of the percentage of participants without abnormal clonal proliferation and polyclonal engraftment . More than 1000 VIS retrieved from peripheral blood should be checked.	0-24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The average Insertion copy number (VCN) in peripheral blood mononuclear cells	The average insertion copy number (VCN) should be ≥0.1 in peripheral blood mononuclear cells	18-24 Months
The expression level of exogenous adult hemoglobin	Exogenous adult hemoglobin will be evaluated by globin chains and hemoglobin synthesis on peripheral blood by HPLC and the exogenous adult hemoglobin level is ≥2.0g/dL	18-24 Months
Change from baseline in annualized frequency of packed RBC transfusions	Compare the annualized number of pRBC transfusions before gene therapy with the Month 18 and Month 24 period after transplant, the percentage change will be recorded	18-24 Months

Collaborators and Investigators

• Sponsor: Shenzhen Hemogen
• Investigators: Principal Investigator: Sixi Liu, Professor, Shenzhen Children's Hospital; Principal Investigator: Chao Liu, PHD, Shenzhen Hemogen

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Estimated): December 30, 2024
• Study Completion (Estimated): May 30, 2025

Study Registration Dates

• First Submitted: February 16, 2023
• First Submitted That Met QC Criteria: February 24, 2023
• First Posted (Actual): February 27, 2023

Study Record Updates

• Last Update Posted (Actual): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

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: SZ-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