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

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

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)

Study Overview

• Status: Enrolling by invitation
• Conditions: Beta-Thalassemia
• Intervention / Treatment: Drug: BRL-101

Detailed Description

This clinical trial is a multi-center, single-arm, single-dose, open-label study without dose escalation. The proposed dose is ≥ 3 × 106 CD34 + cells/kg administered as a single intravenous infusion. The primary objective of Phase 1 is to explore the safety of the study drug in different age groups. For subjects of each age group, myeloablative conditioning and dosing of the remaining subjects was initiated only after completion of dosing and safety observations and assessments in sentinel subjects. The Phase 2 primary objective was to determine the effectiveness of BRL-101 administered intravenously to patients with TDT.

• Study Type: Interventional
• Enrollment (Estimated): 39
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510510
      • Nanfang Hospital, Southern Medical University
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • The First Affiliated Hospital of Guangxi Medical University
  • Hunan
    • Changsha, Hunan, China, 510510
      • Xiangya Hospital of Central South University
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China
      • Chinese Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 35 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BRL-101; 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; CD34 + autologous hematopoietic stem and progenitor cells edited at the BCL11A enhancer site; Other Names: BRL-101 autologous hematopoietic stem and progenitor cells injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of stem cell engrafted subjects	Stem cell engraftment was defined as an absolute peripheral blood neutrophil count of ≥ 0.5 × 109/L for 3 consecutive days within 42 days following BRL-101 intravenous infusion.	Within 42 Days After BRL-101 Infusion
Time to neutrophil engraftment	Defined as Day 1 of absolute peripheral blood neutrophil count ≥ 0.5 × 109/L for 3 consecutive days	Up to 12 Months After BRL-101 Infusion
Frequency, severity, and relationship to BRL-101 of adverse events over 12 months following BRL-101 infusion	Adverse events assessed according to NCI-CTCAE v5.0 criteria	Up to 12 Months After BRL-101 Infusion

Collaborators and Investigators

• Sponsor: Bioray Laboratories
• Collaborators: Xiangya Hospital of Central South University; First Affiliated Hospital of Guangxi Medical University; Nanfang Hospital, Southern Medical University; Chinese Academy of Medical Sciences
• Investigators: Study Chair: Xiaochen Wang, PhD, Bioray Laboratories

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2022
• Primary Completion (Estimated): August 20, 2026
• Study Completion (Estimated): July 10, 2027

Study Registration Dates

• First Submitted: October 9, 2022
• First Submitted That Met QC Criteria: October 9, 2022
• First Posted (Actual): October 13, 2022

Study Record Updates

• Last Update Posted (Estimated): January 13, 2026
• Last Update Submitted That Met QC Criteria: January 12, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Transfusion-Dependent β-Thalassemia
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Thalassemia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; beta-Thalassemia
• Other Study ID Numbers: 2022-BRL-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No