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

NCT05442346 | Suspended

• 1 other identifier: 2021-BRL-103
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Thalassemia Major

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (12)

• Proportion of subjects achieving sustained transfusion independence for at least 3 months (TI3)

  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

Other Outcomes (2)

• 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

Study Arms (1)

γ-globin reactivated autologous hematopoietic stem cells

EXPERIMENTAL

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

Biological: γ-globin reactivated autologous hematopoietic stem cells

Interventions

γ-globin reactivated autologous hematopoietic stem cells BIOLOGICAL

gene edited autologous hematopoietic stem cells with γ-globin expression; BRL-103

γ-globin reactivated autologous hematopoietic stem cells

Eligibility Criteria

• Age: 3 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Bioray Laboratories: lead
• First Affiliated Hospital of Guangxi Medical University: collaborator

Study Sites (1)

Shanghai Bioray Laboratories Inc

Shanghai, Shanghai Municipality, 200241, China

Location

MeSH Terms

Conditions

beta-Thalassemia

Condition Hierarchy (Ancestors)

Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• lai yongrong, PhD

  First Affiliated Hospital of Guangxi Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2021
• First Posted: July 5, 2022
• Study Start: December 25, 2023
• Primary Completion: September 8, 2024
• Study Completion: November 30, 2024
• Last Updated: February 28, 2024

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: data will be available before 2023.10.1, one week long
• Access Criteria: university and institute

Locations

CN (1)