Safety and Efficacy Evaluation of BRL-101 in Subjects With Transfusion-Dependent β-Thalassemia

Study Overview
=================
Brief Summary
-----------------
This is a non-randomized, open label, multi-site, single-dose, phase 1/2 study in subjects with Transfusion-Dependent β-Thalassemia (TDT). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) (BRL-101)

Official Title
-----------------
A Phase 1/2 Clinical Study to Evaluate the Safety and Efficacy of Single Dose Intravenous Infusion of BRL-101 in Subjects With Transfusion-Dependent β-Thalassemia

Conditions
-----------------
Beta-Thalassemia

Intervention / Treatment
-----------------
* Drug: BRL-101


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Fully understand and voluntarily sign informed consent. 3-35years old. At least one legal guardian and/or Subjects to sign informed consent. Clinically diagnosed as β-thalassemia major, phenotypes including β0β0, β+β+, β+β0, βEβ0 genotype. Subjects with no affection with HIV, TP, HBV, HCV, CMV and EBV. Subjects body condition eligible for autologous stem cell transplant. Key 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. Prior hematopoietic stem cell transplant (HSCT). Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 3 Years
Maximum Age: 35 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BRL-101<br>BRL-101 (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene). Subjects will receive a single infusion of BRL-101. | Drug: BRL-101<br>* BRL-101 autologous hematopoietic stem and progenitor cells injection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects achieving successful neutrophil engraftment within 42 days after BRL-101 infusion |  | Within 42 Days After BRL-101 Infusion | 
| Time to neutrophil engraftment |  | Up to 12 Months After BRL-101 Infusion | 
| Time to platelet engraftment |  | Up to 12 Months After BRL-101 Infusion | 
| Incidence of Transplant-related Mortality (TRM) Within 100 Days and 12 months after BRL-101Infusion |  | Within 100 days and 12 months After BRL-101 Infusion | 
| Frequency, severity, and relationship to BRL-101 of adverse events over 12 months following BRL-101 infusion |  | Up to 12 Months After BRL-101 Infusion | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Transfusion-Dependent β-Thalassemia