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

NCT04211480 | Completed

• 1 other identifier: 2019-BRL-00CH1
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This is a non-randomized, open label, single-dose, phase 1/2 study in up to 12 participants with β-thalassemia major.This study aims to evaluate the safety and efficacy of the treatment with γ-globin reactivated autologous hematopoietic stem cells in subjects with β-thalassemia major.

Conditions

β Thalassemia Major

Outcome Measures

Primary Outcomes (2)

• Safety evaluation of γ-globin reactivated autologous hematopoietic stem cells

  Proportion of subjects with engraftment; Overall survival.

  up to 24 months post transplant

• Incidence and severity of adverse events as a measure of safety and tolerability. Adverse events assessed according to NCI-CTCAE v5.0 criteria

  Incidence of AEs and SAEs post transplant

  up to 24 months post transplant

Secondary Outcomes (1)

• Efficacy evaluation of γ-globin reactivated autologous hematopoietic stem cells

  up 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

γ-globin reactivated autologous hematopoietic stem cells

Eligibility Criteria

• Age: 5 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Fully understand and voluntarily sign informed consent. 5-15years old. At least one legal guardian and/or Subjects to sign informed consent.
• Clinically diagnosed as β-thalassemia major, phenotypes including β0β0, 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
• Xiangya Hospital of Central South University: collaborator
• The 923rd Hospital of Joint Logistics Support Force of People's Liberation Army: collaborator

Study Sites (1)

Shanghai Bioray Laboratories Inc.

Shanghai, Shanghai Municipality, 200241, China

Location

Related Publications (2)

• Fu B, Liao J, Chen S, Li W, Wang Q, Hu J, Yang F, Hsiao S, Jiang Y, Wang L, Chen F, Zhang Y, Wang X, Li D, Liu M, Wu Y. CRISPR-Cas9-mediated gene editing of the BCL11A enhancer for pediatric beta0/beta0 transfusion-dependent beta-thalassemia. Nat Med. 2022 Aug;28(8):1573-1580. doi: 10.1038/s41591-022-01906-z. Epub 2022 Aug 4.

  PMID: 35922667 DERIVED

• Brusson M, Miccio A. Genome editing approaches to beta-hemoglobinopathies. Prog Mol Biol Transl Sci. 2021;182:153-183. doi: 10.1016/bs.pmbts.2021.01.025. Epub 2021 Mar 1.

  PMID: 34175041 DERIVED

Study Officials

• Bin Fu, Prof.

  Xiangya Hospital Central 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: December 23, 2019
• First Posted: December 26, 2019
• Study Start: October 1, 2020
• Primary Completion: October 15, 2023
• Study Completion: November 27, 2023
• Last Updated: January 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: IPD sharing will begin at 6 months and end at 36 months following article publication.
• Access Criteria: IPD will be shared with investigators for individual data meta-analysis, after their proposed use of the data has been approved by an independent review committee. Proposals should be directed to yxwu@bio.ecnu.edu.cn and fu.bin@csu.edu.cn. To gain access, data requestors will need to sign a data access agreement.

Locations

CN (1)