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

Beta-Thalassemia Clinical Trial

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05577312
• Other study ID #: 2022-BRL-101
• Status: Enrolling by invitation
• Phase: Phase 1
• Start date: November 1, 2022
• Est. completion date: September 10, 2026

Study information

• Verified date: January 2024
• Source: Bioray Laboratories
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 9
• Est. completion date: September 10, 2026
• Est. primary completion date: August 4, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 35 Years

Eligibility

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 ß-thalassemia major, phenotypes including ß0ß0, ß+ß+, ß+ß0, ßEß0 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.

Related Conditions & MeSH terms

• Beta-Thalassemia
• Thalassemia

Intervention

Drug:
• BRL-101
CD34 + autologous hematopoietic stem and progenitor cells edited at the BCL11A enhancer site

Locations

Country	Name	City	State
China	Xiangya Hospital of Central South University	Changsha	Hunan
China	Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	Chinese Academy of Medical Sciences	Tianjin	Tianjin

Sponsors (5)

Lead Sponsor	Collaborator
Bioray Laboratories	Chinese Academy of Medical Sciences, First Affiliated Hospital of Guangxi Medical University, Nanfang Hospital, Southern Medical University, Xiangya Hospital of Central South University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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