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

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

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.

Study Overview

• Status: Suspended
• Conditions: Thalassemia Major
• Intervention / Treatment: Biological: γ-globin reactivated autologous hematopoietic stem cells

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.

• Study Type: Interventional
• Enrollment (Estimated): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200241
      • Shanghai Bioray Laboratories Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 35 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

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: γ-globin reactivated autologous hematopoietic stem cells; each subject will accept one dose of γ-globin reactivated autologous hematopoietic stem cells	Biological: γ-globin reactivated autologous hematopoietic stem cells; gene edited autologous hematopoietic stem cells with γ-globin expression; BRL-103

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects achieving successful neutrophil engraftment within 42 days after BRL-103 infusion		From 12 months to 24 months post transplant
Time to neutrophil engraftment		From 12 months to 24 months post transplant
Time to platelet engraftment		From 12 months to 24 months post transplant
Frequency and severity of adverse events through 100 days after BRL-103 Infusion		From 12 months to 24 months post transplant
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	From 12 months to 24 months post transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	From 12 months to 24 months post transplant
Proportion of subjects achieving TR6		From 12 months to 24 months post transplant
Proportion of subjects achieving TR12		From 12 months to 24 months post transplant
Proportion of subjects achieving sustained transfusion independence for at least 6 months (TI6)		From 12 months to 24 months post transplant
Proportion of subjects achieving sustained transfusion independence for at least 12 months (TI12)		From 12 months to 24 months post transplant
Incidence of transplant related mortality (TRM) within 100 days and within 1 year		From 12 months to 24 months post transplant
Frequency, severity, and relationship to BRL-103 of adverse events over two years following BRL-103 infusion.		From 12 months to 24 months post transplant
All-cause mortality		From 12 months to 24 months post transplant
Proportion of alleles with intended genetic modification present in peripheral blood leukocytes over time		From 12 months to 24 months post transplant
Fetal hemoglobin concentration (pre-transfusion) over time		From 12 months to 24 months post transplant
Total hemoglobin concentration (pre-transfusion) over time		From 12 months to 24 months post transplant
Change in serum ferritin level from baseline over time		From 12 months to 24 months post transplant

Other Outcome Measures

Outcome Measure	Time Frame
Changes in the proportion of red blood cells expressing HbF in the blood circulation	From 12 months to 24 months post transplant
LDH levels over time	From 12 months to 24 months post transplant

Collaborators and Investigators

• Sponsor: Bioray Laboratories
• Collaborators: First Affiliated Hospital of Guangxi Medical University
• Investigators: Principal Investigator: lai yongrong, PhD, First Affiliated Hospital of Guangxi Medical University

Study record dates

Study Major Dates

• Study Start (Actual): December 25, 2023
• Primary Completion (Estimated): September 8, 2024
• Study Completion (Estimated): November 30, 2024

Study Registration Dates

• First Submitted: September 23, 2021
• First Submitted That Met QC Criteria: June 30, 2022
• First Posted (Actual): July 5, 2022

Study Record Updates

• Last Update Posted (Estimated): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: July 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: 2021-BRL-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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