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

A Single Center, Open Label Study to Evaluate the Safety and Efficacy of β-globin Restored Autologous Hematopoietic Stem Cells in ß-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: Not yet recruiting
• Conditions: β-Thalassemia Major
• Intervention / Treatment: Biological: β-globin restored autologous HSC

Detailed Description

Subjects with ß-Thalassemia major will be recruited and their autologous hematopoietic stem cells will be collected and modified with LentiHBBT87Q system to restore the β-globin expression. After conditioning, the β-globin restored autologous hematopoietic stem cells will be infused back to patients, and a 2 years follow up visit will be conducted and the data will be collected. Participants in this study will be also asked to participant in a subsequent follow up study that will monitor the long-term safety and efficacy of the treatment for up to 13 years post-transplantation.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jing Li, PhD; Phone Number: 13510560664; Email: lijing4@genomics.cn

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518083
      • Beijing Genomics Institute At Shenzhen
      • Contact: Jing Li, PhD; Phone Number: +8613510560664; Email: lijing4@genomics.cn
      • Principal Investigator: Chao LIU, PhD
      • Principal Investigator: Sixi Liu, Professor

Participation Criteria

Eligibility Criteria

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

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; 10 transfusion dependent β-thalassemia major subjects who are 8-16 years older will be transplanted with β-globin restored autologous hematopoietic stem cells that are modified with lentiviral vector LentiHBBT87Q encoding the human β-globin gene.	Biological: β-globin restored autologous HSC; β-globin restored autologous HSC modified with lentiviral vector 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 engraftments	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 at 6, 12, 18 and 24 months after transplant. 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 and volume of packed RBC transfusions	Compare the annualized number of pRBC transfusions before gene therapy with the Month 6 and Month 24 period after transplant, the percentage change will be recorded.	18-24 Months

Collaborators and Investigators

• Sponsor: BGI-research
• Collaborators: Shenzhen Children's Hospital
• Investigators: Principal Investigator: Chao Liu, PhD, BGI-research; Principal Investigator: Sixi Liu, Professor, Shenzhen Children's Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2020
• Primary Completion (Anticipated): November 30, 2022
• Study Completion (Anticipated): November 30, 2024

Study Registration Dates

• First Submitted: September 30, 2020
• First Submitted That Met QC Criteria: October 13, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Actual): October 19, 2020
• Last Update Submitted That Met QC Criteria: October 13, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: β-thalassemia major; β-globin restoration; autologous HSCT
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Thalassemia; beta-Thalassemia
• Other Study ID Numbers: A-SOP-CT-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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