Clinical trial NCT04211480: Safety and Efficacy Evaluation of γ-globin Reactivated Autologous Hematopoietic Stem Cells
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: β Thalassemia Major
Lead sponsor: Bioray Laboratories
Sponsor class: INDUSTRY
Collaborators: name: Xiangya Hospital of Central South University
name: The 923rd Hospital of Joint Logistics Support Force of People's Liberation Army
First posted: 2019-12-26
Enrollment: 6
Sex: ALL
Minimum age (years): 5
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety evaluation of γ-globin reactivated autologous hematopoietic stem cells
timeFrame: up to 24 months post transplant
measure: Incidence and severity of adverse events as a measure of safety and tolerability. Adverse events assessed according to NCI-CTCAE v5.0 criteria
timeFrame: up to 24 months post transplant
Secondary outcomes:
measure: Efficacy evaluation of γ-globin reactivated autologous hematopoietic stem cells
timeFrame: up to 24 months post transplant
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Bioray Laboratories Inc.
state: Shanghai
Study officials:
affiliation: Xiangya Hospital Central University
name: Bin Fu, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.