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

Sponsor

Bioray Laboratories (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04211480

Collaborator

Xiangya Hospital of Central South University (Other), PLA 923 Hospital (Other)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
β Thalassemia Major	Biological: γ-globin reactivated autologous hematopoietic stem cells	N/A

Detailed Description

γ-globin reactivated 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

Anticipated Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 1, 2020

Anticipated Primary Completion Date :

Aug 15, 2022

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: γ-globin reactivated autologous hematopoietic stem cells each subject will accept one dose of γ-globin reactivated autologous hematopoietic stem cells	Biological: γ-globin reactivated autologous hematopoietic stem cells gene edited autologous hematopoietic stem cells with γ-globin expression

Arm

Intervention/Treatment

Experimental: γ-globin reactivated autologous hematopoietic stem cells

each subject will accept one dose of γ-globin reactivated autologous hematopoietic stem cells

Biological: γ-globin reactivated autologous hematopoietic stem cells

gene edited autologous hematopoietic stem cells with γ-globin expression

Outcome Measures

Primary Outcome Measures

Safety evaluation of γ-globin reactivated autologous hematopoietic stem cells [up to 24 months post transplant]
Proportion of subjects with engraftment; Overall survival.
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 24 months post transplant]
Incidence of AEs and SAEs post transplant

Secondary Outcome Measures

Efficacy evaluation of γ-globin reactivated autologous hematopoietic stem cells [up to 24 months post transplant]
Proportion of subjects achieving transfusion independence for at least 6 months (TI6); Proportion of subjects achieving TI12; Proportion of alleles with intended genetic modification in bone marrow cells; Change in total hemoglobin concentration; Change from baseline in annualized frequency and volume of packed RBC transfusions.

Eligibility Criteria

Criteria

Ages Eligible for Study:

5 Years to 15 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Shanghai Bioray Laboratories Inc.	Shanghai	Shanghai	China	200241

Sponsors and Collaborators

Bioray Laboratories
Xiangya Hospital of Central South University
PLA 923 Hospital

Investigators

Principal Investigator: Bin Fu, Prof., Xiangya Hospital Central University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Bioray Laboratories

ClinicalTrials.gov Identifier:

NCT04211480

Other Study ID Numbers:

2019-BRL-00CH1

First Posted:

Dec 26, 2019

Last Update Posted:

Jun 8, 2022

Last Verified:

Jun 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Thalassemia

beta-Thalassemia

Study Results

No Results Posted as of Jun 8, 2022