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

Tracking Information

• First Submitted Date: September 23, 2021
• First Posted Date: July 5, 2022
• Last Update Posted Date: February 28, 2024
• Actual Study Start Date: December 25, 2023
• Estimated Primary Completion Date: September 8, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 1, 2022)

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

Original Primary Outcome Measures (submitted: June 30, 2022)

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

Current Secondary Outcome Measures (submitted: June 30, 2022)

• 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
• Proportion of subjects achieving TR6 [ Time Frame: From 12 months to 24 months post transplant ]
• Proportion of subjects achieving TR12 [ Time Frame: From 12 months to 24 months post transplant ]
• Proportion of subjects achieving sustained transfusion independence for at least 6 months (TI6) [ Time Frame: From 12 months to 24 months post transplant ]
• Proportion of subjects achieving sustained transfusion independence for at least 12 months (TI12) [ Time Frame: From 12 months to 24 months post transplant ]
• Incidence of transplant related mortality (TRM) within 100 days and within 1 year [ Time Frame: 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. [ Time Frame: From 12 months to 24 months post transplant ]
• All-cause mortality [ Time Frame: From 12 months to 24 months post transplant ]
• Proportion of alleles with intended genetic modification present in peripheral blood leukocytes over time [ Time Frame: From 12 months to 24 months post transplant ]
• Fetal hemoglobin concentration (pre-transfusion) over time [ Time Frame: From 12 months to 24 months post transplant ]
• Total hemoglobin concentration (pre-transfusion) over time [ Time Frame: From 12 months to 24 months post transplant ]
• Change in serum ferritin level from baseline over time [ Time Frame: From 12 months to 24 months post transplant ]

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: June 30, 2022)

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

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• 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
• 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.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Thalassemia Major

Intervention

Biological: γ-globin reactivated autologous hematopoietic stem cells

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

Study Arms

Experimental: γ-globin reactivated autologous hematopoietic stem cells

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

Intervention: Biological: γ-globin reactivated autologous hematopoietic stem cells

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Suspended
• Estimated Enrollment (submitted: June 30, 2022): 5
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 30, 2024
• Estimated Primary Completion Date: September 8, 2024 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 3 Years to 35 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT05442346
• Other Study ID Numbers: 2021-BRL-103
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

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

• Current Responsible Party: Bioray Laboratories
• Original Responsible Party: Same as current
• Current Study Sponsor: Bioray Laboratories
• Original Study Sponsor: Same as current
• Collaborators: First Affiliated Hospital of Guangxi Medical University

Investigators

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

• PRS Account: Bioray Laboratories
• Verification Date: July 2023