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

Thalassemia Major Clinical Trial

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT05442346
• Other study ID #: 2021-BRL-103
• Status: Suspended
• Phase: N/A
• Start date: December 25, 2023
• Est. completion date: November 30, 2024

Study information

• Verified date: July 2023
• Source: Bioray Laboratories
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 5
• Est. completion date: November 30, 2024
• Est. primary completion date: September 8, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 35 Years

Eligibility

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 ß-thalassemia major, phenotypes including ß0ß0, ß+ß+?ß

+ß0, ßEß0 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

Related Conditions & MeSH terms

• beta-Thalassemia
• Thalassemia
• Thalassemia Major

Intervention

Biological:
• ?-globin reactivated autologous hematopoietic stem cells
gene edited autologous hematopoietic stem cells with ?-globin expression; BRL-103

Locations

Country	Name	City	State
China	Shanghai Bioray Laboratories Inc	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Bioray Laboratories	First Affiliated Hospital of Guangxi Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in the proportion of red blood cells expressing HbF in the blood circulation		From 12 months to 24 months post transplant
Other	LDH levels over time		From 12 months to 24 months post transplant
Primary	Proportion of subjects achieving successful neutrophil engraftment within 42 days after BRL-103 infusion		From 12 months to 24 months post transplant
Primary	Time to neutrophil engraftment		From 12 months to 24 months post transplant
Primary	Time to platelet engraftment		From 12 months to 24 months post transplant
Primary	Frequency and severity of adverse events through 100 days after BRL-103 Infusion		From 12 months to 24 months post transplant
Primary	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	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
Secondary	Proportion of subjects achieving TR6		From 12 months to 24 months post transplant
Secondary	Proportion of subjects achieving TR12		From 12 months to 24 months post transplant
Secondary	Proportion of subjects achieving sustained transfusion independence for at least 6 months (TI6)		From 12 months to 24 months post transplant
Secondary	Proportion of subjects achieving sustained transfusion independence for at least 12 months (TI12)		From 12 months to 24 months post transplant
Secondary	Incidence of transplant related mortality (TRM) within 100 days and within 1 year		From 12 months to 24 months post transplant
Secondary	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
Secondary	All-cause mortality		From 12 months to 24 months post transplant
Secondary	Proportion of alleles with intended genetic modification present in peripheral blood leukocytes over time		From 12 months to 24 months post transplant
Secondary	Fetal hemoglobin concentration (pre-transfusion) over time		From 12 months to 24 months post transplant
Secondary	Total hemoglobin concentration (pre-transfusion) over time		From 12 months to 24 months post transplant
Secondary	Change in serum ferritin level from baseline over time		From 12 months to 24 months post transplant