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

• ClinicalTrials.gov Identifier: NCT05442346
• Recruitment Status: Suspended
• First Posted: July 5, 2022
• Last Update Posted: February 28, 2024
• Sponsor: Bioray Laboratories
• Collaborator: First Affiliated Hospital of Guangxi Medical University
• Information provided by (Responsible Party): Bioray Laboratories

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.

Condition or disease	Intervention/treatment	Phase
Thalassemia Major	Biological: γ-globin reactivated autologous hematopoietic stem cells	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: December 25, 2023
• Estimated Primary Completion Date: September 8, 2024
• Estimated Study Completion Date: November 30, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Proportion of subjects achieving successful neutrophil engraftment within 42 days after BRL-103 infusion [ Time Frame: From 12 months to 24 months post transplant ]
2. Time to neutrophil engraftment [ Time Frame: From 12 months to 24 months post transplant ]
3. Time to platelet engraftment [ Time Frame: From 12 months to 24 months post transplant ]
4. Frequency and severity of adverse events through 100 days after BRL-103 Infusion [ Time Frame: From 12 months to 24 months post transplant ]
5. Proportion of subjects achieving sustained transfusion reduction for at least 3 months (TR3) [ Time Frame: From 12 months to 24 months post transplant ]
   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 :

1. Proportion of subjects achieving sustained transfusion independence for at least 3 months (TI3) [ Time Frame: From 12 months to 24 months post transplant ]
   Routine transfusion without disease related and with Hb ≥ 90 g/L for at least 3 months
2. Proportion of subjects achieving TR6 [ Time Frame: From 12 months to 24 months post transplant ]
3. Proportion of subjects achieving TR12 [ Time Frame: From 12 months to 24 months post transplant ]
4. Proportion of subjects achieving sustained transfusion independence for at least 6 months (TI6) [ Time Frame: From 12 months to 24 months post transplant ]
5. Proportion of subjects achieving sustained transfusion independence for at least 12 months (TI12) [ Time Frame: From 12 months to 24 months post transplant ]
6. Incidence of transplant related mortality (TRM) within 100 days and within 1 year [ Time Frame: From 12 months to 24 months post transplant ]
7. 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 ]
8. All-cause mortality [ Time Frame: From 12 months to 24 months post transplant ]
9. Proportion of alleles with intended genetic modification present in peripheral blood leukocytes over time [ Time Frame: From 12 months to 24 months post transplant ]
10. Fetal hemoglobin concentration (pre-transfusion) over time [ Time Frame: From 12 months to 24 months post transplant ]
11. Total hemoglobin concentration (pre-transfusion) over time [ Time Frame: From 12 months to 24 months post transplant ]
12. Change in serum ferritin level from baseline over time [ Time Frame: From 12 months to 24 months post transplant ]

Other Outcome Measures:

1. Changes in the proportion of red blood cells expressing HbF in the blood circulation [ Time Frame: From 12 months to 24 months post transplant ]
2. LDH levels over time [ Time Frame: From 12 months to 24 months post transplant ]

Eligibility Criteria

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

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

Contacts and Locations

Locations

China, Shanghai

Shanghai Bioray Laboratories Inc

Shanghai, Shanghai, China, 200241

Sponsors and Collaborators

Bioray Laboratories

First Affiliated Hospital of Guangxi Medical University

Investigators

• Principal Investigator: lai yongrong, PhD; First Affiliated Hospital of Guangxi Medical University

More Information

• Responsible Party: Bioray Laboratories
• ClinicalTrials.gov Identifier: NCT05442346
• Other Study ID Numbers: 2021-BRL-103
• First Posted: July 5, 2022
• Last Update Posted: February 28, 2024
• Last Verified: July 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: clinical study protocol will be shared after Estimated Primary Completion Date
• Supporting Materials: Study Protocol
• Time Frame: data will be available before 2023.10.1, one week long
• Access Criteria: university and institute

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Thalassemia; beta-Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn