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

Primary Purpose

β-Thalassemia Major

Status

Not yet recruiting

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

β-globin restored autologous HSC

About this trial

This is an interventional treatment trial for β-Thalassemia Major focused on measuring β-thalassemia major, β-globin restoration, autologous HSCT

Eligibility Criteria

8 Years - 16 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Beijing Genomics Institute At Shenzhen

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Overall survival

Number of patients alive through the whole trial will be record.

Proportion of engraftments

Neutrophil count [ANC] >=500 /mm3 for 3 consecutive days and platelet count [PLT] >20,000/mm3 for7 consecutive days.

Replication competent lentivirus (RCL)

The percentage of RCL should be negative in the 24 months after transplant.

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.

Secondary Outcome Measures

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.

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.

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.

Full Information

NCT ID

NCT04592458

First Posted

September 30, 2020

Last Updated

October 13, 2020

Sponsor

BGI-research

Collaborators

Shenzhen Children's Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04592458

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2020

Overall Recruitment Status

Not yet recruiting

Study Start Date

November 1, 2020 (Anticipated)

Primary Completion Date

November 30, 2022 (Anticipated)

Study Completion Date

November 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

BGI-research

Collaborators

Shenzhen Children's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

β-Thalassemia Major

Keywords

β-thalassemia major, β-globin restoration, autologous HSCT

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Experimental

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

β-globin restored autologous HSC

Intervention Description

β-globin restored autologous HSC modified with lentiviral vector LentiHBBT87Q

Primary Outcome Measure Information:

Title

Frequency and severity of adverse events (AEs) and serious adverse events (SAEs)

Description

The number and the percentage of adverse events related to transplantation in 100 days will be summarized according to NCI CTCAE 5.0.

Time Frame

0-100 days

Title

Overall survival

Description

Number of patients alive through the whole trial will be record.

Time Frame

0-24 months

Title

Proportion of engraftments

Description

Neutrophil count [ANC] >=500 /mm3 for 3 consecutive days and platelet count [PLT] >20,000/mm3 for7 consecutive days.

Time Frame

0-24 months

Title

Replication competent lentivirus (RCL)

Description

The percentage of RCL should be negative in the 24 months after transplant.

Time Frame

0-24 months

Title

Dynamics of viral integration sites (VIS)

Description

Time Frame

0-24 months

Secondary Outcome Measure Information:

Title

The average Insertion copy number (VCN) in peripheral blood mononuclear cells

Description

The average insertion copy number (VCN) should be ≥0.1 in peripheral blood mononuclear cells.

Time Frame

18-24 Months

Title

The expression level of exogenous adult hemoglobin

Description

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.

Time Frame

18-24 Months

Title

Change from baseline in annualized frequency and volume of packed RBC transfusions

Description

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.

Time Frame

18-24 Months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

8 Years

Maximum Age & Unit of Time

16 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jing Li, PhD

Phone

13510560664

lijing4@genomics.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Chao Liu, PhD

Organizational Affiliation

BGI-research

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Sixi Liu, Professor

Organizational Affiliation

Shenzhen Children's Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Beijing Genomics Institute At Shenzhen

City

Shenzhen

State/Province

Guangdong

ZIP/Postal Code

518083

Country

China

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jing Li, PhD

Phone

+8613510560664

lijing4@genomics.cn

First Name & Middle Initial & Last Name & Degree

Chao Liu, PhD

First Name & Middle Initial & Last Name & Degree

Sixi Liu, Professor

12. IPD Sharing Statement

Plan to Share IPD

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

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