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

Phase 1

• Conditions: Beta-Thalassemia
• Interventions: Drug: BRL-101

• Registration Number: NCT05577312
• Lead Sponsor: Bioray Laboratories

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)

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 Timeline

• Study First Submitted: 2022-10-09
• Study First Submitted QC: 2022-10-09
• Study First Posted: 2022-10-13
• Study Start: 2022-11-01
• Status Verified: 2024-01
• Last Update Submitted: 2024-02-29
• Last Update Posted: 2024-03-04
• Primary Completion: 2025-08-04
• Study Completion: 2026-09-10

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 9

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BRL-101	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.

Primary Outcome Measures

Name	Time	Method
Proportion of stem cell engrafted subjects	Within 42 Days After BRL-101 Infusion	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.
Time to neutrophil engraftment	Up to 12 Months After BRL-101 Infusion	Defined as Day 1 of absolute peripheral blood neutrophil count ≥ 0.5 × 109/L for 3 consecutive days
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	Adverse events assessed according to NCI-CTCAE v5.0 criteria

Trial Locations

Locations (4)

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, China

Xiangya Hospital of Central South University; 🇨🇳 Changsha, Hunan, China