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

Tracking Information

• First Submitted Date: December 18, 2019
• First Posted Date: December 19, 2019
• Last Update Posted Date: October 13, 2022
• Actual Study Start Date: November 1, 2021
• Actual Primary Completion Date: June 1, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 2, 2022)

• Proportion of subjects with engraftment; [ Time Frame: 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 [ Time Frame: up to 60 days post transplant ]

• Original Primary Outcome Measures (submitted: December 18, 2019): Incidence and Severity of Adverse Events as a Measure of Safety and Tolerability Adverse events assessed according to NCI-CTCAE v4.03 criteria [ Time Frame: up to 6 months post transplant ]

Current Secondary Outcome Measures (submitted: April 2, 2022)

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

Original Secondary Outcome Measures (submitted: December 18, 2019)

efficacy of γ-globin reactivated autologous hematopoietic stem cells [ Time Frame: 12 months post transplant ]

Independence on blood transfusion after transplantation; Or, The amount of red cell transfusion in a year post transplantation reduced 20% than that of the last year.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: β-globin Restored Autologous HSC in β-thalassemia Major Patients
• Official Title: a Safety and Efficacy Study of β-globin Restored Autologous Hematopoietic Stem Cells for β-thalassemia Major Patients With CVS-654 Mutation
• 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.
• 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
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: β-thalassemia Major

Intervention

Biological: β-globin restored autologous HSC

gene edited autologous hematopoietic stem cells with β-globin restoration

Study Arms

Experimental: β-globin restored autologous HSC

each subject will accept one dose of β-globin restored autologous hematopoietic stem cells

Intervention: Biological: β-globin restored autologous HSC

• 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: October 9, 2022): 2
• Original Estimated Enrollment (submitted: December 18, 2019): 12
• Actual Study Completion Date: July 25, 2022
• Actual Primary Completion Date: June 1, 2022 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 5 Years to 15 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04205435
• Other Study ID Numbers: 2019-BRL-00CH2
• 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: No

• Current Responsible Party: Bioray Laboratories
• Original Responsible Party: Same as current
• Current Study Sponsor: Bioray Laboratories
• Original Study Sponsor: Same as current
• Collaborators: PLA 923 Hospital

Investigators

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

• PRS Account: Bioray Laboratories
• Verification Date: September 2021