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Safety and Efficacy Evaluation of γ-globin Reactivated Autologous Hematopoietic Stem Cells

Primary Purpose

β Thalassemia Major

Status

Active

Phase

Not Applicable

Locations

China

Study Type

Interventional

Intervention

γ-globin reactivated autologous hematopoietic stem cells

About this trial

This is an interventional treatment trial for β Thalassemia Major

Eligibility Criteria

5 Years - 15 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Fully understand and voluntarily sign informed consent. 5-15years old. At least one legal guardian and/or Subjects to sign informed consent.
Clinically diagnosed as β-thalassemia major, phenotypes including β0β0, β+β0,βEβ0 genotype.
Subjects with no affection with EBV, HIV, CMV, TP, HAV, HBV and HCV.
Subjects body condition eligible for autologous stem cell transplant.

Exclusion Criteria:

Subjects acceptable for allogeneic hematopoietic stem cell transplantation and have an available fully matched related donor.
Active bacterial, viral, or fungal infection.
Treated with erythropoietin prior 3 months.
Immediate family member with any known hematological tumor.
Subjects with severe psychiatric disorders to be unable to cooperate.
Recently diagnosed as malaria.
History of complex autoimmune disease.
Persistent aspartate transaminase (AST), alanine transaminase (ALT), or total bilirubin value >3 X the upper limit of normal (ULN).
Subjects with severe heart, lung and kidney diseases.
With serious iron overload, serum ferritin>5000mg/ml.
Any other condition that would render the subject ineligible for HSCT, as determined by the attending transplant physician or Investigator.
Subjects who are receiving treatment from another clinical study, or have received another gene therapy.
Subjects or guardians had resisted the guidance of the attending doctor.
Subjects whom the investigators do not consider appropriate for participating in this clinical study.

Sites / Locations

Shanghai Bioray Laboratories Inc.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

γ-globin reactivated autologous hematopoietic stem cells

Arm Description

each subject will accept one dose of γ-globin reactivated autologous hematopoietic stem cells

Outcomes

Primary Outcome Measures

Safety evaluation of γ-globin reactivated autologous hematopoietic stem cells

Proportion of subjects with engraftment; Overall survival.

Incidence and severity of adverse events as a measure of safety and tolerability. Adverse events assessed according to NCI-CTCAE v5.0 criteria

Incidence of AEs and SAEs post transplant

Secondary Outcome Measures

Efficacy evaluation of γ-globin reactivated autologous hematopoietic stem cells

Proportion of subjects achieving transfusion independence for at least 6 months (TI6); Proportion of subjects achieving TI12; Proportion of alleles with intended genetic modification in bone marrow cells; Change in total hemoglobin concentration; Change from baseline in annualized frequency and volume of packed RBC transfusions.

Full Information

NCT ID

NCT04211480

First Posted

December 23, 2019

Last Updated

October 9, 2022

Sponsor

Bioray Laboratories

Collaborators

Xiangya Hospital of Central South University, The 923rd Hospital of Joint Logistics Support Force of People's Liberation Army

1. Study Identification

Unique Protocol Identification Number

NCT04211480

Brief Title

Safety and Efficacy Evaluation of γ-globin Reactivated Autologous Hematopoietic Stem Cells

Official Title

an Open Label Trial of Evaluation of the Safety and Efficacy of Treatment With γ-globin Reactivated Autologous Hematopoietic Stem Cells in Subjects With β-thalassemia Major

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

April 1, 2020 (Actual)

Primary Completion Date

October 15, 2023 (Anticipated)

Study Completion Date

December 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bioray Laboratories

Collaborators

Xiangya Hospital of Central South University, The 923rd Hospital of Joint Logistics Support Force of People's Liberation Army

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This is a non-randomized, open label, single-dose, phase 1/2 study in up to 12 participants with β-thalassemia major.This study aims to evaluate the safety and efficacy of the treatment with γ-globin reactivated autologous hematopoietic stem cells in subjects with β-thalassemia major.

Detailed Description

γ-globin reactivated autologous hematopoietic stem cells will be manufactured using Crispr/Cas9 gene editing system. Subject participation for this study will be 1 year. Subjects who enroll in this study will be asked to participate in a subsequent long-term follow up study that will monitor the safety and efficacy of the treatment they receive for up to 15 years post-transplant.

6. Conditions and Keywords

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

β Thalassemia Major

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

γ-globin reactivated autologous hematopoietic stem cells

Arm Type

Experimental

Arm Description

each subject will accept one dose of γ-globin reactivated autologous hematopoietic stem cells

Intervention Type

Biological

Intervention Name(s)

γ-globin reactivated autologous hematopoietic stem cells

Intervention Description

gene edited autologous hematopoietic stem cells with γ-globin expression

Primary Outcome Measure Information:

Title

Safety evaluation of γ-globin reactivated autologous hematopoietic stem cells

Description

Proportion of subjects with engraftment; Overall survival.

Time Frame

up to 24 months post transplant

Title

Incidence and severity of adverse events as a measure of safety and tolerability. Adverse events assessed according to NCI-CTCAE v5.0 criteria

Description

Incidence of AEs and SAEs post transplant

Time Frame

up to 24 months post transplant

Secondary Outcome Measure Information:

Title

Efficacy evaluation of γ-globin reactivated autologous hematopoietic stem cells

Description

Time Frame

up to 24 months post transplant

10. Eligibility

Sex

All

Minimum Age & Unit of Time

5 Years

Maximum Age & Unit of Time

15 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Fully understand and voluntarily sign informed consent. 5-15years old. At least one legal guardian and/or Subjects to sign informed consent. Clinically diagnosed as β-thalassemia major, phenotypes including β0β0, β+β0,βEβ0 genotype. Subjects with no affection with EBV, HIV, CMV, TP, HAV, HBV and HCV. Subjects body condition eligible for autologous stem cell transplant. Exclusion Criteria: Subjects acceptable for allogeneic hematopoietic stem cell transplantation and have an available fully matched related donor. Active bacterial, viral, or fungal infection. Treated with erythropoietin prior 3 months. Immediate family member with any known hematological tumor. Subjects with severe psychiatric disorders to be unable to cooperate. Recently diagnosed as malaria. History of complex autoimmune disease. Persistent aspartate transaminase (AST), alanine transaminase (ALT), or total bilirubin value >3 X the upper limit of normal (ULN). Subjects with severe heart, lung and kidney diseases. With serious iron overload, serum ferritin>5000mg/ml. Any other condition that would render the subject ineligible for HSCT, as determined by the attending transplant physician or Investigator. Subjects who are receiving treatment from another clinical study, or have received another gene therapy. Subjects or guardians had resisted the guidance of the attending doctor. Subjects whom the investigators do not consider appropriate for participating in this clinical study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bin Fu, Prof.

Organizational Affiliation

Xiangya Hospital Central University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Shanghai Bioray Laboratories Inc.

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200241

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Individual participant data (IPD) that underlie the results reported in published article will be shared, after deidentification (text, tables,figures and appendices). Other available documents include study protocol.

IPD Sharing Time Frame

IPD sharing will begin at 6 months and end at 36 months following article publication.

IPD Sharing Access Criteria

IPD will be shared with investigators for individual data meta-analysis, after their proposed use of the data has been approved by an independent review committee. Proposals should be directed to yxwu@bio.ecnu.edu.cn and fu.bin@csu.edu.cn. To gain access, data requestors will need to sign a data access agreement.

Citations:

PubMed Identifier

35922667

Citation

Fu B, Liao J, Chen S, Li W, Wang Q, Hu J, Yang F, Hsiao S, Jiang Y, Wang L, Chen F, Zhang Y, Wang X, Li D, Liu M, Wu Y. CRISPR-Cas9-mediated gene editing of the BCL11A enhancer for pediatric beta0/beta0 transfusion-dependent beta-thalassemia. Nat Med. 2022 Aug;28(8):1573-1580. doi: 10.1038/s41591-022-01906-z. Epub 2022 Aug 4.

Results Reference

derived

PubMed Identifier

34175041

Citation

Brusson M, Miccio A. Genome editing approaches to beta-hemoglobinopathies. Prog Mol Biol Transl Sci. 2021;182:153-183. doi: 10.1016/bs.pmbts.2021.01.025. Epub 2021 Mar 1.

Results Reference

derived

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Safety and Efficacy Evaluation of γ-globin Reactivated Autologous Hematopoietic Stem Cells

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