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

Primary Purpose

Thalassemia Major

Status
Suspended
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
γ-globin reactivated autologous hematopoietic stem cells
Sponsored by
Bioray Laboratories
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Thalassemia Major

Eligibility Criteria

3 Years - 35 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Key inclusion criteria:

  • Fully understand and voluntarily sign informed consent. 3-35years old. At least one legal guardian and/or Subjects to sign informed consent.

  • Clinically diagnosed as β-thalassemia major, phenotypes including β0β0, β+β+、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.

Key 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

Proportion of subjects achieving successful neutrophil engraftment within 42 days after BRL-103 infusion
Time to neutrophil engraftment
Time to platelet engraftment
Frequency and severity of adverse events through 100 days after BRL-103 Infusion
Proportion of subjects achieving sustained transfusion reduction for at least 3 months (TR3)
TR3 was defined as at least a 50% reduction in monthly red blood cell transfusion volume and transfusion frequency compared to baseline for at least 3 months

Secondary Outcome Measures

Proportion of subjects achieving sustained transfusion independence for at least 3 months (TI3)
Routine transfusion without disease related and with Hb ≥ 90 g/L for at least 3 months
Proportion of subjects achieving TR6
Proportion of subjects achieving TR12
Proportion of subjects achieving sustained transfusion independence for at least 6 months (TI6)
Proportion of subjects achieving sustained transfusion independence for at least 12 months (TI12)
Incidence of transplant related mortality (TRM) within 100 days and within 1 year
Frequency, severity, and relationship to BRL-103 of adverse events over two years following BRL-103 infusion.
All-cause mortality
Proportion of alleles with intended genetic modification present in peripheral blood leukocytes over time
Fetal hemoglobin concentration (pre-transfusion) over time
Total hemoglobin concentration (pre-transfusion) over time
Change in serum ferritin level from baseline over time

Full Information

First Posted
September 23, 2021
Last Updated
July 21, 2023
Sponsor
Bioray Laboratories
Collaborators
First Affiliated Hospital of Guangxi Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT05442346
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
July 2023
Overall Recruitment Status
Suspended
Why Stopped
Sponsor decision
Study Start Date
December 25, 2023 (Anticipated)
Primary Completion Date
September 8, 2024 (Anticipated)
Study Completion Date
November 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bioray Laboratories
Collaborators
First Affiliated Hospital of Guangxi Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a single arm, open label, single-dose, phase 1/2 study in up to 5 participants with β-thalassemia major.The study will 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 Glycosylase Base Editors. Subject participation for this study will be 2 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
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
5 (Anticipated)

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; BRL-103
Primary Outcome Measure Information:
Title
Proportion of subjects achieving successful neutrophil engraftment within 42 days after BRL-103 infusion
Time Frame
From 12 months to 24 months post transplant
Title
Time to neutrophil engraftment
Time Frame
From 12 months to 24 months post transplant
Title
Time to platelet engraftment
Time Frame
From 12 months to 24 months post transplant
Title
Frequency and severity of adverse events through 100 days after BRL-103 Infusion
Time Frame
From 12 months to 24 months post transplant
Title
Proportion of subjects achieving sustained transfusion reduction for at least 3 months (TR3)
Description
TR3 was defined as at least a 50% reduction in monthly red blood cell transfusion volume and transfusion frequency compared to baseline for at least 3 months
Time Frame
From 12 months to 24 months post transplant
Secondary Outcome Measure Information:
Title
Proportion of subjects achieving sustained transfusion independence for at least 3 months (TI3)
Description
Routine transfusion without disease related and with Hb ≥ 90 g/L for at least 3 months
Time Frame
From 12 months to 24 months post transplant
Title
Proportion of subjects achieving TR6
Time Frame
From 12 months to 24 months post transplant
Title
Proportion of subjects achieving TR12
Time Frame
From 12 months to 24 months post transplant
Title
Proportion of subjects achieving sustained transfusion independence for at least 6 months (TI6)
Time Frame
From 12 months to 24 months post transplant
Title
Proportion of subjects achieving sustained transfusion independence for at least 12 months (TI12)
Time Frame
From 12 months to 24 months post transplant
Title
Incidence of transplant related mortality (TRM) within 100 days and within 1 year
Time Frame
From 12 months to 24 months post transplant
Title
Frequency, severity, and relationship to BRL-103 of adverse events over two years following BRL-103 infusion.
Time Frame
From 12 months to 24 months post transplant
Title
All-cause mortality
Time Frame
From 12 months to 24 months post transplant
Title
Proportion of alleles with intended genetic modification present in peripheral blood leukocytes over time
Time Frame
From 12 months to 24 months post transplant
Title
Fetal hemoglobin concentration (pre-transfusion) over time
Time Frame
From 12 months to 24 months post transplant
Title
Total hemoglobin concentration (pre-transfusion) over time
Time Frame
From 12 months to 24 months post transplant
Title
Change in serum ferritin level from baseline over time
Time Frame
From 12 months to 24 months post transplant
Other Pre-specified Outcome Measures:
Title
Changes in the proportion of red blood cells expressing HbF in the blood circulation
Time Frame
From 12 months to 24 months post transplant
Title
LDH levels over time
Time Frame
From 12 months to 24 months post transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key inclusion criteria: Fully understand and voluntarily sign informed consent. 3-35years old. At least one legal guardian and/or Subjects to sign informed consent. Clinically diagnosed as β-thalassemia major, phenotypes including β0β0, β+β+、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. Key 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
lai yongrong, PhD
Organizational Affiliation
First Affiliated Hospital of Guangxi Medical 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
clinical study protocol will be shared after Estimated Primary Completion Date
IPD Sharing Time Frame
data will be available before 2023.10.1, one week long
IPD Sharing Access Criteria
university and institute

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

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