Clinical trial NCT04205435: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: β-thalassemia Major
Lead sponsor: Bioray Laboratories
Sponsor class: INDUSTRY
Collaborators: name: The 923rd Hospital of Joint Logistics Support Force of People's Liberation Army
First posted: 2019-12-19
Enrollment: 2
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 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.

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.

Primary outcomes:
measure: Proportion of subjects with engraftment;
timeFrame: up to 42 days 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 60 days post transplant
Secondary outcomes:
measure: Proportion of subjects achieving transfusion independence;
timeFrame: up to 24 months post transplant
measure: Proportion of subjects with a > = 50% reduced annualized volume of packed RBC transfusions.
timeFrame: up to 24 months post transplant
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Bioraylaboratory Inc
state: Shanghai
Study officials:
affiliation: The 923rd Hospital of Joint Logistics Support Force of People's Liberation Army
name: Xinhua Zhang, Prof
role: PRINCIPAL_INVESTIGATOR
References:
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.