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

• ClinicalTrials.gov Identifier: NCT04205435
• Recruitment Status: Terminated
• First Posted: December 19, 2019
• Last Update Posted: October 13, 2022
• Sponsor: Bioray Laboratories
• Collaborator: PLA 923 Hospital
• Information provided by (Responsible Party): Bioray Laboratories

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
β-thalassemia Major	Biological: β-globin restored autologous HSC	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: a Safety and Efficacy Study of β-globin Restored Autologous Hematopoietic Stem Cells for β-thalassemia Major Patients With CVS-654 Mutation
• Actual Study Start Date: November 1, 2021
• Actual Primary Completion Date: June 1, 2022
• Actual Study Completion Date: July 25, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Proportion of subjects with engraftment; [ Time Frame: up to 42 days post transplant ]
2. Incidence and severity of adverse events as a measure of safety and tolerability. Adverse events assessed according to NCI-CTCAE v5.0 criteria [ Time Frame: up to 60 days post transplant ]

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 5 Years to 15 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

China, Shanghai

Shanghai Bioraylaboratory Inc

Shanghai, Shanghai, China, 200241

Sponsors and Collaborators

Bioray Laboratories

PLA 923 Hospital

Investigators

• Principal Investigator: Xinhua Zhang, Prof; PLA 923 Hospital

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Bioray Laboratories
• ClinicalTrials.gov Identifier: NCT04205435
• Other Study ID Numbers: 2019-BRL-00CH2
• First Posted: December 19, 2019
• Last Update Posted: October 13, 2022
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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