Clinical trial NCT05442346: 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
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: NA
Conditions: Thalassemia Major
Lead sponsor: Bioray Laboratories
Sponsor class: INDUSTRY
Collaborators: name: First Affiliated Hospital of Guangxi Medical University
First posted: 2022-07-05
Enrollment: 5
Sex: ALL
Minimum age (years): 3
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Proportion of subjects achieving successful neutrophil engraftment within 42 days after BRL-103 infusion
timeFrame: From 12 months to 24 months post transplant
measure: Time to neutrophil engraftment
timeFrame: From 12 months to 24 months post transplant
measure: Time to platelet engraftment
timeFrame: From 12 months to 24 months post transplant
measure: Frequency and severity of adverse events through 100 days after BRL-103 Infusion
timeFrame: From 12 months to 24 months post transplant
measure: Proportion of subjects achieving sustained transfusion reduction for at least 3 months (TR3)
timeFrame: From 12 months to 24 months post transplant
Secondary outcomes:
measure: Proportion of subjects achieving sustained transfusion independence for at least 3 months (TI3)
timeFrame: From 12 months to 24 months post transplant
measure: Proportion of subjects achieving TR6
timeFrame: From 12 months to 24 months post transplant
measure: Proportion of subjects achieving TR12
timeFrame: From 12 months to 24 months post transplant
measure: Proportion of subjects achieving sustained transfusion independence for at least 6 months (TI6)
timeFrame: From 12 months to 24 months post transplant
measure: Proportion of subjects achieving sustained transfusion independence for at least 12 months (TI12)
timeFrame: From 12 months to 24 months post transplant
measure: Incidence of transplant related mortality (TRM) within 100 days and within 1 year
timeFrame: From 12 months to 24 months post transplant
measure: Frequency, severity, and relationship to BRL-103 of adverse events over two years following BRL-103 infusion.
timeFrame: From 12 months to 24 months post transplant
measure: All-cause mortality
timeFrame: From 12 months to 24 months post transplant
measure: Proportion of alleles with intended genetic modification present in peripheral blood leukocytes over time
timeFrame: From 12 months to 24 months post transplant
measure: Fetal hemoglobin concentration (pre-transfusion) over time
timeFrame: From 12 months to 24 months post transplant
measure: Total hemoglobin concentration (pre-transfusion) over time
timeFrame: From 12 months to 24 months post transplant
measure: Change in serum ferritin level from baseline over time
timeFrame: From 12 months to 24 months post transplant
Other outcomes:
measure: Changes in the proportion of red blood cells expressing HbF in the blood circulation
timeFrame: From 12 months to 24 months post transplant
measure: LDH levels over time
timeFrame: From 12 months to 24 months post transplant
Locations:
city: Shanghai
country: China
facility: Shanghai Bioray Laboratories Inc
state: Shanghai
Study officials:
affiliation: First Affiliated Hospital of Guangxi Medical University
name: lai yongrong, PhD
role: PRINCIPAL_INVESTIGATOR
References: