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

Phase 2Enrolling By InvitationNCT05577312

Bioray Laboratories39 enrolled

Overview

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)

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Beta-Thalassemia

Interventions

BRL-101DRUG

CD34 + autologous hematopoietic stem and progenitor cells edited at the BCL11A enhancer site

Eligibility

Sex: ALLMin age: 3 YearsMax age: 35 Years

Medical Language ↔ Plain English

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.

Locations (4)

Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, China

The First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, China

Xiangya Hospital of Central South University

Changsha, Hunan, China

Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, China

Outcomes

Primary Outcomes

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.

Time frame: 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

Time frame: 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

Time frame: Up to 12 Months After BRL-101 Infusion

Data from ClinicalTrials.gov

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