β-globin Restored Autologous HSC in β-thalassemia Major Patients

a Safety and Efficacy Study of β-globin Restored Autologous Hematopoietic Stem Cells for β-thalassemia Major Patients With CVS-654 Mutation

This is a single center, single arm, open-label study to determine the safety and efficacy of β-globin restored autologous hematopoietic stem cells in β- thalassemia major patients with CVS-654 mutation.

Study Overview

• Status: Terminated
• Conditions: β-thalassemia Major
• Intervention / Treatment: Biological: β-globin restored autologous HSC

Detailed Description

β-globin restored autologous hematopoietic stem cells will be manufactured using CRISPR/Cas9 gene editing system. Subject participation for this study will be 1 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
• Enrollment (Actual): 2
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200241
      • Shanghai Bioraylaboratory Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 15 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 5-15 years old. Clinically diagnosed as β-thalassemia major with IVS-654 gene mutation phenotype;
• Subjects or at least one legal guardian/agent understand and voluntarily sign informed consent.
• Subjects with no affection with EBV, HIV, CMV, TP, HAV, HBV and HCV.
• Subjects body condition eligible for autologous stem cell transplant.

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. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: β-globin restored autologous HSC; each subject will accept one dose of β-globin restored autologous hematopoietic stem cells	Biological: β-globin restored autologous HSC; gene edited autologous hematopoietic stem cells with β-globin restoration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects with engraftment;	up to 42 days 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	up to 60 days post transplant

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects achieving transfusion independence;	up to 24 months post transplant
Proportion of subjects with a > = 50% reduced annualized volume of packed RBC transfusions.	up to 24 months post transplant

Collaborators and Investigators

• Sponsor: Bioray Laboratories
• Collaborators: PLA 923 Hospital
• Investigators: Principal Investigator: Xinhua Zhang, Prof, PLA 923 Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2021
• Primary Completion (ACTUAL): June 1, 2022
• Study Completion (ACTUAL): July 25, 2022

Study Registration Dates

• First Submitted: December 18, 2019
• First Submitted That Met QC Criteria: December 18, 2019
• First Posted (ACTUAL): December 19, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 13, 2022
• Last Update Submitted That Met QC Criteria: October 9, 2022
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Thalassemia; beta-Thalassemia
• Other Study ID Numbers: 2019-BRL-00CH2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No